Culture of Care has been an integral part of Sanofi's policy on animal protection for more than 15 years. Culture of Care goes beyond compliance with regulations and standards, since it relates to the attitudes of staff and to caring for research animals, as well as to the company's commitment to an active animal protection policy. However, the concept of Culture of Care remains subjective. Via two anonymous and voluntary surveys conducted in 2018 and 2021, it was possible to understand the level of staff engagement and the perception of company efficiency. Based on key questions, it was possible to assess individual engagement (animal welfare knowledge, pride, engagement, recognition) and company commitments (oversight body efficiency, level of transparency, Sanofi policy on animal protection). The institutional scores were 7.7/10 and 7.9/10 obtained in 2018 and in 2021, respectively. The individual score obtained for 2018 was 6.7/10 compared to 6.9/10 obtained in 2021. The combination of these two criteria helps to determine a Culture of Care score and thus make it a performance indicator. The scores are CoC2018 (7.7; 6.7) and CoC2021 (7.9; 6.9). Being able to quantify this level of engagement and the perception that employees have of the company encourages the organisation of an improvement programme and helps measure the benefits.

Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points.

Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.

Ticagrelor has multiple indications, including for some patients with chronic coronary syndromes (CCS) at high risk of ischaemic events. Body mass can potentially affect pharmacodynamics (PD) and pharmacokinetics (PK). We investigated the influence of body mass (range 53-172 kg, 20.8-46.9 kg/m2) on PD/PK in 221 CCS patients receiving ticagrelor 60 mg or 90 mg twice-daily (BD) during two randomised-controlled trials. Correlations between body weight (BW) or body mass index (BMI) and PD/PK measurements obtained during maintenance treatment at trough ('pre-dose') and peak effect ('post-dose') were assessed. BW and BMI correlated with P2Y12 reactivity units at pre-dose (e.g. BW:R = 0.26, p = 0.008) but not post-dose timepoints. BW affected ticagrelor active metabolite (TAM) levels (e.g. 60 mg BD, post-dose:R = -0.39, p < 0.0001) and there was evidence of an inverse power law relationship between BW and TAM-to-ticagrelor ratio. PK with ticagrelor 60 mg correlated significantly with BMI. BW and BMI did not affect the chance of high platelet reactivity, which remained very low across the whole cohort. There was no difference in PRU between the two doses of ticagrelor within each weight or BMI group. Body mass has modest effects on the PK/PD response to ticagrelor in patients with CCS but currently-used regimens appear adequate across the range of BW/BMI studied.

We assessed the impact of the first wave of COVID-19 pandemic on non-COVID hospital admissions, non-COVID mortality, factors associated with non-COVID mortality, and changes in the profile of non-COVID patients admitted to hospital. We used the Spanish Minimum Basic Data Set with diagnosis grouped according to the Diagnostic Related Groups. A total of 10,594 patients (3% COVID-19; 97% non-COVID) hospitalised during the first wave in 2020 (27-February/07-June) were compared with those hospitalised within the same dates of 2017-2019 (average annual admissions: 14,037). We found a decrease in non-COVID medical (22%) and surgical (33%) hospitalisations and a 25.7% increase in hospital mortality among non-COVID patients during the first pandemic wave compared to pre-pandemic years. During the officially declared sub-period of excess mortality in the area (17-March/20-April, in-hospital non-COVID mortality was even higher (58.7% higher than the pre-pandemic years). Non-COVID patients hospitalised during the first pandemic wave (compared to pre-pandemic years) were older, more frequently men, with longer hospital stay and increased disease severity. Hospitalisation during the first pandemic wave in 2020, compared to hospitalisation during the pre-pandemic years, was an independent risk factor for non-COVID mortality (HR 1.30, 95% CI 1.07-1.57, p = 0.008), reflecting the negative impact of the pandemic on hospitalised patients.

The management of asthma has changed fundamentally during the past two decades. Precise assessment and phenotyping are now required to establish individually targeted treatment with disease-modifying anti-asthmatic drugs (DMAADs). Patients with asthma are often managed by primary care doctors or non-respiratory specialists in secondary care. However, the implementation of complex asthma guidelines in non-specialised care remains a challenge. There is a need for easy-to-understand, concise guides for general practice. In this Viewpoint, we propose a one-page practical guide for asthma management, titled A2BCD, with four components: dual assessment (A2) of asthma (ie, diagnosis and phenotype, plus asthma control and future risks); basic measures (B; eg, education, self-management skills, regular physical activity, and avoidance of asthma triggers); identification and treatment of comorbidities (C) of asthma (eg, chronic rhinosinusitis, obesity, or sleep apnoea); and phenotype-specific, individually targeted treatment with DMAADs (D), including individual inhalation schemes based on inhaled corticosteroids, leukotriene modifiers, biologics, and allergen immunotherapy.

In drug research, developing a sound understanding of the key mechanistic drivers of pharmacokinetics (PK) for new molecular entities is essential for human PK and dose predictions. Here, characterizing the absorption, distribution, metabolism, and excretion (ADME) processes is crucial for a mechanistic understanding of the drug-target and drug-body interactions. Sufficient knowledge on ADME processes enables reliable interspecies and human PK estimations beyond allometric scaling. The physiologically based PK (PBPK) modeling framework allows the explicit consideration of organ-specific ADME processes. The sum of all passive and active ADME processes results in the observed plasma PK. Gene expression information can be used as surrogate for protein abundance and activity within PBPK models. The absolute and relative expression of ADME genes can differ between species and strains. This is affecting both, the PK and pharmacodynamics and is therefore posing a challenge for the extrapolation from preclinical findings to humans. We developed an automated workflow that generates whole-body gene expression databases for humans and other species relevant in drug development, animal health, nutritional sciences, and toxicology. Solely, bulk RNA-seq data curated and provided by the Swiss Institute of Bioinformatics from healthy, normal, and untreated primary tissue samples were considered as an unbiased reference of normal gene expression. The databases are interoperable with the Open Systems Pharmacology Suite (PK-Sim and MoBi) and enable seamless access to a central source of curated cross-species gene expression data. This will increase data transparency, increase reliability and reproducibility of PBPK model simulations, and accelerate mechanistic PBPK model development in the future.

Although the understanding of secondary progressive multiple sclerosis (SPMS) is evolving, early detection of relapse-independent progression remains difficult. This is further complicated by superimposed relapses and compensatory mechanisms that allow for silent progression. The term relapsing multiple sclerosis (RMS) subsumes relapsing-remitting multiple sclerosis (RRMS) and SPMS with relapses. The latter is termed 'active' SPMS, for which disease-modifying therapies (DMTs) approved for either RMS or active SPMS can be used. However, the level of evidence supporting efficacy and safety in SPMS differs between drugs approved for RMS and SPMS. Our review aims to identify current evidence from published clinical trials and European public assessment reports from the marketing authorization procedure on the efficacy, especially on progression, of DMTs approved for RMS and SPMS. To identify relevant evidence, a literature search has been conducted and European public assessment reports of DMTs approved for RMS have been screened for unpublished data specific to SPMS. Only two clinical trials demonstrated a significant reduction in disability progression in SPMS study populations: the EXPAND study for siponimod, which included a typical SPMS population, and the European study for interferon (IFN)-beta 1b s.c., which included patients with very early and active SPMS. Both DMTs also achieved significant reductions in relapse rates. Ocrelizumab, cladribine, ofatumumab, and ponesimod are all approved for RMS - ocrelizumab, ofatumumab, and ponesimod based on an RMS study, cladribine based on an RRMS study. Data on efficacy in SPMS are only available from post hoc analyses of very small subgroups, representing only up to 15% of the total study population. For these DMTs, approval for RMS, including active SPMS, was mainly based on the assumption that the reduction in relapse rate observed in patients with RRMS can also be applied to SPMS. Based on that, the potential of these drugs to reduce relapse-independent progression remains unclear.

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MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.

Colorectal cancer (CRC) is the third cause of cancer death worldwide. Although, in some cases, treatment can increase patient survival and reduce cancer recurrence, in many cases, tumors can develop resistance to therapy leading to recurrence. One of the main reasons for recurrence and therapy resistance is the presence of cancer stem cells (CSCs). CSCs possess a self-renewal ability, and their stemness properties lead to the avoidance of apoptosis, and allow a new clone of cancer cells to emerge. Numerous investigations inidicated the involvment of cellular signaling pathways in embryonic development, and growth, repair, and maintenance of tissue homeostasis, also participate in the generation and maintenance of stemness in colorectal CSCs. This review discusses the role of Wnt, NF-κB, PI3K/AKT/mTOR, Sonic hedgehog, and Notch signaling pathways in colorectal CSCs, and the possible modulating drugs that could be used in treatment for resistant CRC.