[Evaluation of the relevance of the pharmaceutical educational interview on the knowledge and satisfaction of patients who received a vagus nerve neurostimulator implantation]. / Évaluation de la pertinence de l'entretien pharmaceutique éducatif sur les connaissances et la satisfaction de patients ayant bénéficié d'une implantation d'un neurostimulateur du nerf vague.

INTRODUCTION: Vagal neurostimulation (VNS) medical devices (MDs) are used to treat drug-resistant epilepsy. Using a magnet, the patient can activate on the stimulations in order to stop a seizure or interrupt the adverse effects (AEs) of the device. The objective is to evaluate the improvement of the patients' knowledge about the VNS following a pharmaceutical educational interview (PEI) as well as their satisfaction. MATERIALS AND METHODS: The pharmaceutical educational interview regarding drugs and DMs was performed by the clinical pharmacist at the patient's bed after VNS implantation. A questionnaire about VNS devices (operation, adverse effects, recommendations) and assessing knowledge was submitted to patients before and after the PEI. Satisfaction was assessed by the Likert scale. RESULTS: From March 2020 to August 2021, 18 implanted patients were included in the study. In 78% of cases (14/18), the total number of good responses after PEI increased. The mean good response was significantly increased from 16.11/25 (64%) before PEI to 22.33/25 (89%) after PEI (P-value<0.01). The maximum satisfaction score (4/4) was given in 71% of the items. DISCUSSION-CONCLUSION: The results support the relevance of PEI. Patients feel a need for information and consider the interview useful. An improvement in knowledge was observed, which allows us to hope for an optimization of the effectiveness of the device, in particular, a reduction in seizures and AE. This study shows the feasibility and the interest of the development of clinical pharmacy applied to medical devices in complementarity with the expertise on drugs.

Age-Related Shift in Cardiac and Metabolic Phenotyping Linked to Inflammatory Cytokines and Antioxidant Status in Mice.

Age-related alterations in cardiac function, metabolic, inflammatory and antioxidant profiles are associated with an increased risk of cardiovascular mortality and morbidity. Here, we examined cardiac and metabolic phenotypes in relation to inflammatory status and antioxidant capacity in young, middle-aged and old mice. Real-time reverse transcription-polymerase chain reactions were performed on myocardium and immunoassays on plasma. Left ventricular (LV) structure and function were assessed by echocardiography using high-frequency ultrasound. Middle-aged mice exhibited an altered metabolic profile and antioxidant capacity compared to young mice, whereas myocardial expression of inflammatory factors (TNFα, IL1ß, IL6 and IL10) remained unchanged. In contrast, old mice exhibited increased expression of inflammatory cytokines and plasma levels of resistin compared to young and middle-aged mice (p < 0.05). The pro-inflammatory signature of aged hearts was associated with alterations in glutathione redox homeostasis and elevated contents of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation and oxidative stress. Furthermore, echocardiographic parameters of LV systolic and diastolic functions were significantly altered in old mice compared to young mice. Taken together, these findings suggest age-related shifts in cardiac phenotype encompass the spectrum of metabo-inflammatory abnormalities and altered redox homeostasis.

Mechanical Thrombectomy with Intravenous Thrombolysis versus Thrombolysis Alone for the Treatment of Stroke: A Systematic Review of Economic Evaluations.

Mechanical thrombectomy has revolutionized the management of stroke by improving the recanalization rates and reducing deleterious consequences. It is now the standard of care despite the high financial cost. A considerable number of studies have evaluated its cost effectiveness. Therefore, this study aimed to identify economic evaluations of mechanical thrombectomy with thrombolysis compared with thrombolysis alone to provide an update of existing evidence, focusing on the period after proof of effectiveness of mechanical thrombectomy. Twenty-one studies were included in the review: 18 were model-based economic evaluations to simulate long-term outcomes and costs, and 19 were conducted in high-income countries. Incremental cost-effectiveness ratios ranged from -$5,670 to $74,216 per quality-adjusted life year. Mechanical thrombectomy is cost-effective in high-income countries and in the populations selected for clinical trials. However, most of the studies used the same data. There is a lack of real-world and long-term data to analyze the cost effectiveness of mechanical thrombectomy in treating the global burden of stroke.

Mortality rate after coronary revascularization in heart failure patients with coronary artery disease.

AIMS: Coronary artery disease (CAD) is a common cause of heart failure (HF). It remains unclear who, when and why to direct towards coronary revascularization. The outcomes of coronary revascularization in HF patients are still a matter of debate nowadays. This study aims to evaluate the effect of revascularization strategy on all-cause of death in the context of ischaemic HF. METHODS AND RESULTS: An observational cohort was conducted on 692 consecutive patients who underwent coronary angiography at the University Hospital of Toulouse between January 2018 and December 2021 for either a recent diagnosis of HF or a decompensated chronic HF, and in whom coronary angiograms showed at least 50% obstructive coronary lesion. The study population was divided into two groups according to the performance or not of a coronary revascularization procedure. The living status (alive or dead) of each of the study's participants was observed by April 2022. Seventy-three per cent of the study population underwent coronary revascularization either by percutaneous coronary intervention (66.6%) or coronary artery bypass grafting (6.2%). Baseline characteristics including age, sex and cardiovascular risk factors did not differ between the invasive and conservative groups, respectively. Death occurred in 162 study participants resulting in an all-cause mortality rate of 23.5%; 26.7% of observed deaths have occurred in the conservative group versus 22.2% in the invasive group (P = 0.208). No difference in survival outcomes has been observed over a mean follow-up period of 2.5 years (P = 0.140) even after stratification by HF categories (P = 0.132) or revascularization modalities (P = 0.366). CONCLUSIONS: Findings from the present study showed comparable all-cause mortality rates between groups. Coronary revascularization does not modify short-term survival outcomes in HF patients compared with optimal medical therapy alone outside the setting of acute coronary syndrome.

Metformin Attenuates Postinfarction Myocardial Fibrosis and Inflammation in Mice.

Diabetes is a major risk factor for the development of cardiovascular disease with a higher incidence of myocardial infarction. This study explores the role of metformin, a first-line antihyperglycemic agent, in postinfarction fibrotic and inflammatory remodeling in mice. Three-month-old C57BI/6J mice were submitted to 30 min cardiac ischemia followed by reperfusion for 14 days. Intraperitoneal treatment with metformin (5 mg/kg) was initiated 15 min after the onset of reperfusion and maintained for 14 days. Real-time PCR was used to determine the levels of COL3A1, αSMA, CD68, TNF-α and IL-6. Increased collagen deposition and infiltration of macrophages in heart tissues are associated with upregulation of the inflammation-associated genes in mice after 14 days of reperfusion. Metformin treatment markedly reduced postinfarction fibrotic remodeling and CD68-positive cell population in mice. Moreover, metformin resulted in reduced expression of COL3A1, αSMA and CD68 after 14 days of reperfusion. Taken together, these results open new perspectives for the use of metformin as a drug that counteracts adverse myocardial fibroticand inflammatory remodeling after MI.

Satisfaction, Usability, and Compliance With the Use of Smartwatches for Ecological Momentary Assessment of Knee Osteoarthritis Symptoms in Older Adults: Usability Study.

BACKGROUND: Smartwatches enable physicians to monitor symptoms in patients with knee osteoarthritis, their behavior, and their environment. Older adults experience fluctuations in their pain and related symptoms (mood, fatigue, and sleep quality) that smartwatches are ideally suited to capture remotely in a convenient manner. OBJECTIVE: The aim of this study was to evaluate satisfaction, usability, and compliance using the real-time, online assessment and mobility monitoring (ROAMM) mobile app designed for smartwatches for individuals with knee osteoarthritis. METHODS: Participants (N=28; mean age 73.2, SD 5.5 years; 70% female) with reported knee osteoarthritis were asked to wear a smartwatch with the ROAMM app installed. They were prompted to report their prior night's sleep quality in the morning, followed by ecological momentary assessments (EMAs) of their pain, fatigue, mood, and activity in the morning, afternoon, and evening. Satisfaction, comfort, and usability were evaluated using a standardized questionnaire. Compliance with regard to answering EMAs was calculated after excluding time when the watch was not being worn for technical reasons (eg, while charging). RESULTS: A majority of participants reported that the text displayed was large enough to read (22/26, 85%), and all participants found it easy to enter ratings using the smartwatch. Approximately half of the participants found the smartwatch to be comfortable (14/26, 54%) and would consider wearing it as their personal watch (11/24, 46%). Most participants were satisfied with its battery charging system (20/26, 77%). A majority of participants (19/26, 73%) expressed their willingness to use the ROAMM app for a 1-year research study. The overall EMA compliance rate was 83% (2505/3036 responses). The compliance rate was lower among those not regularly wearing a wristwatch (10/26, 88% vs 16/26, 71%) and among those who found the text too small to read (4/26, 86% vs 22/26, 60%). CONCLUSIONS: Older adults with knee osteoarthritis positively rated the ROAMM smartwatch app and were generally satisfied with the device. The high compliance rates coupled with the willingness to participate in a long-term study suggest that the ROAMM app is a viable approach to remotely collecting health symptoms and behaviors for both research and clinical endeavors.

From hospitalisation to primary care: integrative model of clinical pharmacy with patients implanted with a PICC line-research protocol for a prospective before-after study.

INTRODUCTION: Clinical pharmacy improves patient safety and secures drug management using information, education and good clinical practices. However, medical device management is still unexplored, and proof of effectiveness is needed. A PICC line (peripherally inserted central catheter) is a medical device for infusion. It accesses the central venous system after being implanted in a peripheral vein. However, complications after implantation often interfere with smooth execution of the treatment. We hypothesise that clinical pharmacy for medical devices could be as effective as clinical pharmacy for medications. The main objective is to assess the effectiveness of clinical pharmacy activities on the complication rate after PICC line implantation. METHODS AND ANALYSIS: This is a before-after prospective study. The study will begin with an observational period without clinical pharmacy activities, followed by an interventional period where pharmacists will intervene on drug and medical device management and provide personalised follow-up and advice. Sixty-nine adult patients will be recruited in each 6-month period from all traditional care units. The main inclusion criteria will be the implantation of a PICC line. The primary outcome is the decrease in the number of complications per patient and per month. Secondary outcomes are the consultation and hospital readmission rates, the acceptance rate of pharmaceutical interventions, the patients' quality of life, the direct hospital induced or avoided costs and the participants' satisfaction. Data will be collected using case report forms during hospitalisation and telephone follow-up after discharge. The analysis will compare these criteria during the two periods. ETHICS AND DISSEMINATION: The study has received the approval of our Ethics Committee (Clermont-Ferrand Southeast VI, France, number AU1586). Results will be made available to the patients or their caregivers, the sponsor and other researchers when asked, as described in the consent form. TRIAL REGISTRATION NUMBER: NCT04359056.

ICP and Antihypertensive Drugs.

OBJECTIVES: Arterial hypertension is among the leading risks for mortality. This burden requires in hypertensive patients the use of single, double or more antihypertensive drugs. The relationship between intracranial pressure (ICP) and arterial blood pressure is complex and still under debate. The impact of antihypertensive drugs on ICP is unknown. We wanted to understand whether the use of antihypertensive drugs has a significant influence on ICP and cerebrospinal fluid (CSF)/brain related parameters. MATERIALS AND METHODS: In a cohort of 95 patients with suspected normal pressure hydrocephalus, we prospectively collected drug details according to the Anatomical Therapeutic Chemical (ATC) classification. Lumbar infusion studies were performed. Using ICM+ software, we calculated at baseline and plateau ICP and pulse amplitude, resistance to CSF outflow, elastance, and pressure in the sagittal sinus and CSF production rate. We studied the influence of the administration of 1, 2, 3 or more antihypertensive drugs on ICP-derived parameters. We compared the data using Student's and Mann-Whitney tests or Chi-squared and Fisher's exact test. RESULTS: Elastance is significantly higher in patients with at least one antihypertensive drug compared with patients without medication. On the contrary, pressure volume index (PVI) is significantly decreased in patients with antihypertensive drugs compared with patients not on these medications. However, the number of antihypertensive drugs does not seem to influence other ICP parameters. CONCLUSIONS: Patients on antihypertensive drugs seem to have a stiffer brain than those not on them.

Mentoring and supervising clinical pharmacist students at patients' bedside: which benefits?

RATIONALE, AIMS AND OBJECTIVES: Hospital clinical pharmacists are involved in teaching students during professional internship. Organization between the unit care and the pharmacy place is complicated. This study evaluated the effectiveness of two pharmaceutical teams: an experienced pharmacist in the pharmacy place, reachable by phone (team 1) or an experienced pharmacist in the ward, near patients and students (team 2). METHODS: Pharmaceutical interventions were collected during two successive time periods, each of 6 months in a 15-bed unit (neurology). During the first time period, prescriptions were analyzed by the student (resident) in the ward and experienced pharmacist in the pharmacy place. During the second time period, prescriptions were analyzed by both experienced pharmacist and the resident in the ward. We compared the number, the type, the approval of pharmaceutical interventions and the medication reconciliation activities. Proportions were compared by a chisquared test (or Fisher exact test) as well as the quantitative value was calculated by a Student test. RESULTS: 'Mentoring and supervising' students in the ward increased significantly the number of pharmaceutical interventions (PI; 104 interventions for 1408 analyzed prescriptions (7.4%) by the students in the ward and 317 interventions for 1391 (22.8%) by both the experienced pharmacist and the students in the ward (P = 0.002). Furthermore, specific interventions from medication reconciliation were significantly increased by the presence of experienced pharmacist in the ward (0.96% vs. 8.83% P = 0.018). CONCLUSION: Effectiveness of clinical pharmacists can be improved by the presence of experienced pharmacist at patients' bedside, near students.

Platelet activation and arterial peripheral serotonin turnover in cardiac remodeling associated to aortic stenosis.

Peripheral serotonin (5-HT) has been involved in adverse cardiac remodeling and valve fibrosis. The peripheral levels of 5-HT mainly depend on its release from activated platelets and degradation by monoamine oxidase A (MAO-A). The SERAOPI study investigated the relationship between arterial serotoninergic system, degree of platelet activation and cardiac remodeling, in patients with aortic valve stenosis (AS). Thirty patients with severe AS and 15 control subjects underwent transthoracic echocardiography, radial, and aortic arterial blood sampling. Measurements of 5-HT and its MAO-A-dependent degradation product, 5-HIAA, were performed by HPLC. Arterial platelet activation was assessed by flow cytometry analysis of platelet surface expression of P-selectin and activated integrin GPIIb/IIIa. Activated platelets and arterial plasma 5-HT increased in AS patients as compared to control subjects (P-selectin 1.08 ± 0.2MFI vs. 0.49 ± 0.1MFI, P = 0.04; GPIIb/IIIa 0.71 ± 0.1MFI vs. 0.35 ± 0.1MFI; P = 0.0015 and arterial plasma 5-HT 11.55 ± 1.6 nM vs. 6.18 ± 0.7 nM, P = 0.028, respectively). Moreover, 5-HT was strongly correlated to left ventricular hypertrophy assessed by echocardiography. The correlation was independent of cardiovascular risk comorbidities and others echocardiographic AS parameters. Finally, plasma 5-HIAA increased in AS patients (74.64 ± 9.7 nM vs. 37.16 ± 4.1 nM; P = 0.0002) indicating a higher 5-HT degradation rate by MAO-A. Platelet activation, arterial circulating serotonin, and serotonin degradation increased in patients with AS. These observations suggest that the serotoninergic system may contribute to the pathogenesis of AS including valve fibrosis and adverse ventricular remodeling.

Potentially inappropriate drug prescribing and associated factors in nursing homes.

IMPORTANCE: Polymedication is frequent in nursing home (NH) residents. This increases the risk of potentially inappropriate drug prescribing (PIDP), which can lead to adverse drug events, such as falls and hospitalization. OBJECTIVE: To identify PIDP in NH residents and to investigate subject-related and NH structural and organizational factors associated with PIDP. DESIGN: Cross-sectional study. SETTING: A total of 175 NHs in Midi-Pyrénées region, South-Western France. PARTICIPANTS: A total of 974 subjects randomly selected from the 6275 NH residents participating in the IQUARE study. EXPOSURE: Patients with PIDP. MAIN OUTCOMES AND MEASURES: PIDP was the main outcome measure. It was defined using a specific indicator, based on the Summary of Product Characteristics, on the Laroche list, and on residents' clinical data. PIDP was defined as the presence of at least 1 of the following criteria: (1) drug with an unfavorable benefit-to-risk ratio; (2) drug with questionable efficacy according to the Laroche list; (3) absolute contraindication; (4) significant drug-drug interaction. Associated factors were identified by using multivariable logistic regression models. RESULTS: Among the 974 residents included, 71% had PIDP. PIDP was more frequent in patients without dementia, with several comorbidities and taking multiple medications. In the multivariable analysis, age (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.01-1.03) and Charlson Comorbidity Index (CCI; P = .003, CCI = 1 versus 0: OR1/0 1.22; 95% CI 0.85-1.74, CCI ≥ 2 versus 0: OR2/0 1.72; 95% CI 1.23-2.41) were associated with an increased likelihood of PIDP. By contrast, dementia was associated with a lower likelihood of PIDP (OR 0.70; 95% CI 0.53-0.94). Among NH structural and organizational characteristics, the access to psychiatric advice and/or to hospitalization in a psychiatric unit (OR 1.36; 95% CI 1.02-1.82) and the presence of a reevaluation of drug prescriptions (OR 1.45; 95% CI 1.07-1.96) were associated with an increased likelihood of PIDP. CONCLUSIONS AND RELEVANCE: Our work suggests that some NH characteristics are associated with an increased likelihood of PIDP. Gaining a better understanding of the factors influencing PIDP, especially structural and organizational NH factors, can help to determine the interventions that should be implemented.

Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment.

Three-dimensional (3D) scaffolds hold great potential for stem cell-based therapies. Indeed, recent results have shown that biomimetic scaffolds may enhance cell survival and promote an increase in the concentration of therapeutic cells at the injury site. The aim of this work was to engineer an original polymeric scaffold based on the respective beneficial effects of alginate and chitosan. Formulations were made from various alginate/chitosan ratios to form opposite-charge polyelectrolyte complexes (PECs). After freeze-drying, the resultant matrices presented a highly interconnected porous microstructure and mechanical properties suitable for cell culture. In vitro evaluation demonstrated their compatibility with mesenchymal stell cell (MSC) proliferation and their ability to maintain paracrine activity. Finally, the in vivo performance of seeded 3D PEC scaffolds with a polymeric ratio of 40/60 was evaluated after an acute myocardial infarction provoked in a rat model. Evaluation of cardiac function showed a significant increase in the ejection fraction, improved neovascularization, attenuated fibrosis as well as less left ventricular dilatation as compared to an animal control group. These results provide evidence that 3D PEC scaffolds prepared from alginate and chitosan offer an efficient environment for 3D culturing of MSCs and represent an innovative solution for tissue engineering.

Cardiac fibroblasts regulate sympathetic nerve sprouting and neurocardiac synapse stability.

Sympathetic nervous system (SNS) plays a key role in cardiac homeostasis and its deregulations always associate with bad clinical outcomes. To date, little is known about molecular mechanisms regulating cardiac sympathetic innervation. The aim of the study was to determine the role of fibroblasts in heart sympathetic innervation. RT-qPCR and western-blots analysis performed in cardiomyocytes and fibroblasts isolated from healthy adult rat hearts revealed that Pro-Nerve growth factor (NGF) and pro-differentiating mature NGF were the most abundant neurotrophins expressed in cardiac fibroblasts while barely detectable in cardiomyocytes. When cultured with cardiac fibroblasts or fibroblast-conditioned medium, PC12 cells differentiated into/sympathetic-like neurons expressing axonal marker Tau-1 at neurites in contact with cardiomyocytes. This was prevented by anti-NGF blocking antibodies suggesting a paracrine action of NGF secreted by fibroblasts. When co-cultured with cardiomyocytes to mimic neurocardiac synapse, differentiated PC12 cells exhibited enhanced norepinephrine secretion as quantified by HPLC compared to PC12 cultured alone while co-culture with fibroblasts had no effect. However, when supplemented to PC12-cardiomyocytes co-culture, fibroblasts allowed long-term survival of the neurocardiac synapse. Activated fibroblasts (myofibroblasts) isolated from myocardial infarction rat hearts exhibited significantly higher mature NGF expression than normal fibroblasts and also promoted PC12 cells differentiation. Within the ischemic area lacking cardiomyocytes and neurocardiac synapses, tyrosine hydroxylase immunoreactivity was increased and associated with local anarchical and immature sympathetic hyperinnervation but tissue norepinephrine content was similar to that of normal cardiac tissue, suggesting depressed sympathetic function. Collectively, these findings demonstrate for the first time that fibroblasts are essential for the setting of cardiac sympathetic innervation and neurocardiac synapse stability. They also suggest that neurocardiac synapse functionality relies on a triptych with tight interaction between sympathetic nerve endings, cardiomyocytes and fibroblasts. Deregulations of this triptych may be involved in pathophysiology of cardiac diseases.

Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

Serotonin (5-HT) regulates different cardiac functions by acting directly on cardiomyocytes, fibroblasts and endothelial cells. Today, it is widely accepted that activated platelets represent a major source of 5-HT. In contrast, a supposed production of 5-HT in the heart is still controversial. To address this issue, we investigated the expression and localization of 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and L-aromatic amino acid decarboxylase (AADC) in the heart. We also evaluated their involvement in cardiac production of 5-HT. TPH1 was weakly expressed in mouse and rat heart and appeared restricted to mast cells. Degranulation of mast cells by compound 48/80 did not modify 5-HT cardiac content in mice. Western blots and immunolabelling experiments showed an abundant expression of AADC in the mouse and rat heart and its co-localization with endothelial cells. Incubation of cardiac homogenate with the AADC substrate (5-hydroxy-L-tryptophan) 5-HTP or intraperitoneal injection of 5-HTP in mice significantly increased cardiac 5-HT. These effects were prevented by the AADC inhibitor benserazide. Finally, 5-HTP administration in mice increased phosphorylation of aortic nitric oxide synthase 3 at Ser (1177) as well as accumulation of nitrates in cardiac tissue. This suggests that the increase in 5-HT production by AADC leads to activation of endothelial and cardiac nitric oxide pathway. These data show that endothelial AADC plays an important role in cardiac synthesis of 5-HT and possibly in 5-HT-dependent regulation of nitric oxide generation.