Attributes for a discrete-choice experiment on preferences of patients for oncology pharmacy consultations.

PURPOSE: To ensure the safe use of oral anticancer drugs, oncology pharmacy consultations (OPCs) have been established in France. They are conditioned by the needs, expectations, and involvement of the patients in their care. Thus, it is essential to elicit their preferences. The discrete-choice experiment (DCE) is a method recommended by the ISPOR for such a task. The "selection and validation of attributes and their values" step is fundamental in this process. In this context, the aim of this study was to present our research approach to identify and validate the attributes that characterize an OPC and their values. METHODS: Due to the lack of relevant published data in the literature, the focus-group method was used in accordance with good research practices for the application of conjoint-analysis of the ISPOR. The two-round Delphi method was used to validate the attributes and their values identified by the focus-group method. RESULTS: The focus-group method enabled identification of nine attributes. Thirty-seven healthcare professionals at a national level, including 30 pharmacists and seven physicians, were selected to take part in the Delphi procedure. Seven attributes (frequency, planification, operation mode, duration, content, written support, and report) and their values were thus validated. CONCLUSION: Based on these results, the next step will be to elicit patient preferences for OPCs and to then shed light on the issues of pharmaceutical support for patients by comparing their preferences with those of informal caregivers and, in particular, those of the healthcare professionals involved in their care.

Evaluation of the interest to combine a CD4 Th1-inducer cancer vaccine derived from telomerase and atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: a randomized non-comparative phase II study (TERTIO - PRODIGE 82).

BACKGROUND: Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non-small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. METHODS: Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. DISCUSSION: Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. TRIAL REGISTRATION: NCT05528952.

Oral therapy adherence and satisfaction in patients with multiple myeloma.

The transition to oral therapies in patients with multiple myeloma (MM) offers potential benefits to patients; however, they must self-manage their medication and adherence plays an important role in patient care. It has been shown that patient satisfaction with their medication has a strong positive correlation with adherence in chronic diseases. The aim of this study was to estimate adherence rate of oral antimyeloma therapies and to identify risk factors for medication non-adherence. This observational, prospective, and multicentre survey based on a self-report questionnaire enrolled MM patients with at least 3 months of oral therapy. The 6-item Girerd scale and the medication possession ratio (MPR) were used for measuring medication adherence and the SATMED-Q® questionnaire was used for measuring satisfaction. An analysis of risk factors for non-adherence to oral therapy was performed using univariate analysis. A total of 101 patients participated in the survey, yielding a response rate of 87%. The prevalence of adherence to oral antimyeloma therapy was estimated at 51.5% using the Girerd questionnaire. According to the MPR, adherence was evaluated at 96% (i.e. MPR ≥ 0.80). Both methods combined, adherence was estimated at 50.5%. One risk factor for medication non-adherence was identified: Eastern Cooperative Oncology Group Performance Status > 2 (p = 0.007). One predictive factor for high medication adherence was identified: high satisfaction with treatment (p = 0.01). Identifying patients at higher risk for non-adherence allows clinical pharmacists to personalise therapeutic information and education and to improve the quality of healthcare overall.

Patient Preferences for Pharmacy Services: A Systematic Review of Studies Based on Discrete Choice Experiments.

BACKGROUND AND OBJECTIVE: In recent years, the mission of pharmacists has evolved and the model of the caregiver-patient relationship has been challenged by a new patient-centered approach. A challenge to providing personalized care is the assessment of patient preferences. We aimed to systematically identify published discrete choice experiments related to patient preferences for pharmacy services and to assess the quality of the selected articles. METHODS: A systematic review of the literature was conducted in two databases (PubMed and Embase, until March 2023) according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The quality of the selected articles was assessed according to the International Society for Pharmacoeconomics and Outcomes Research conjoint analysis checklist. RESULTS: Among the 421 articles identified, 16 published studies were included and analyzed. They were mostly published in pharmaceutical (n = 6), economic (n = 4), and public health (n = 4) journals. Only two articles concerned the field of hospital pharmacy. Only five presented the specific pharmacy service studied: filling of prescriptions, management of symptoms, treatment delivery, and components of pharmacist counseling. Five articles focused on pharmacy services related to a specific disease. None fully fulfilled the International Society for Pharmacoeconomics and Outcomes Research checklist, only partially fulfilled. CONCLUSIONS: According to the identified studies, cost, time, logistics (organizational criteria), and pharmacists' courtesy and skills were consistently cited as factors influencing patient preferences for pharmacy services. The disclosure of patient preferences is a complex and under-researched topic, especially in the field of pharmacy, but interest is growing. As the mission of pharmacists evolves to bring them closer to patients, the better understanding of patient preferences in pharmacy services will allow for better targeting and better integration of patient profiles in patient management.

Terminal Care in Parkinson's Disease: Real-Life Use of Continuous Subcutaneous Apomorphine Infusion to Improve Patient Comfort.

BACKGROUND: There are currently no recommendations on the therapeutic management of Parkinson's disease (PD) patients at the end of life. OBJECTIVE: To describe a cohort of patients with PD who benefited from continuous subcutaneous apomorphine infusion (CSAI) initiation at the end of their life as comfort care. METHODS: This real-life cohort includes 14 PD patients, who benefited from 24-h, low-dose CSAI (0.5-3 mg/h) in the context of terminal care. Patient's comfort (pain, rigidity, and/or ability to communicate) and occurrence of CSAI-related side-effects (nausea/vomiting, cutaneous and behavioral manifestations) were evaluated based on medical records. RESULTS: All patients (age 62-94 years, disease duration 2-32 years) presented with late-stage PD and a compromised oral route. Treatment lasted from a few hours to 39 days. CSAI led to substantial functional improvement, with a good safety profile. Overall clinical comfort was deemed improved by the medical team, the patient, and/or caregivers. CONCLUSIONS: CSAI might be a promising approach in PD terminal care, as it reduces motor symptoms and overall discomfort, with an apparent good safety profile. Use of the apomorphine pen, sublingual film or a classic syringe pump might be considered when apomorphine pumps are not available. Larger observational cohorts and randomized controlled trials are needed to establish the efficacy and tolerability of apomorphine in the context of terminal care and more broadly, in an advance care planning perspective.

[Causes of medication administration errors in elderly people: a systematic review]. / Causes des erreurs médicamenteuses à l'administration chez la personne âgée : une revue de la littérature.

The elderly are particularly vulnerable to medication administration errors (MAE). To prevent these errors, it is crucial to identify and understand their causes. A review of the literature using the PRISMA method was conducted. Of 2,798 articles, 15 were included in the literature review. The causes identified were divided into 4 categories: patient-related, direct drug-related, healthcare professional-related, and organizational, teamwork, and environmental causes. It was found that the causes were many and varied (n = 56). These were mostly related to physical and cognitive disorders of the patient. Few studies of causes based on empirical data were conducted on this specific subject. The majority of studies were conducted in a health care facility and institution. Therefore, this study cannot provide a comprehensive review of all the risk factors for MAE, especially in the elderly who are capable of administering their medication on their own. To study this topic, a complementary literature review on the causes of non-adherence in the elderly would be necessary.

Enhancing collaboration between geriatricians, oncologists, and pharmacists to optimize medication therapy in older adults with cancer: A position paper from SOFOG-SFPO.

Optimizing anticancer treatment and medication therapy in older patients with cancer requires a multidisciplinary approach, with a strong collaboration between geriatricians, oncologists and pharmacists. While all patients can benefit, some clinical situations seem to be high-priority. Careful attention should be given to patients with cardiovascular comorbidities and/or diabetes, which are prone to decompensate during anticancer treatment and often involve multiple medications. Another great concern is the risk of falls, closely related to polypharmacy, hence the need for a comprehensive medication review. Managing the pharmacological treatment of depression is also challenging and require shared expertise. Finally, pharmacists can prove valuable in situations of adherence difficulties or use of complementary medicines. Collaborative practice should begin at initiation of anticancer treatment and continue throughout the care pathway, as continuous reassessment is essential. Although the integration of pharmacists in multidisciplinary teams is often challenged by funding, collaborative should still be strongly encouraged.

Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study.

PURPOSE: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year. RESULTS: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders (P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders (P = .005), respectively. CONCLUSION: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

Impact of pharmacist medication review for paediatric patients: an observational study.

BACKGROUND: Paediatric patients are at high risk of medication errors and adverse drug events due to complex medical care. OBJECTIVE: To assess the impact of pharmacist medication review for paediatric patients. SETTING: A single-centre prospective observational study was performed over 33 months, from February 2018 to October 2020 in a French Hospital. METHOD: Clinical pharmacists provided medication counselling at a hospital and conducted telephone follow-ups between 3 and 7 days after discharge of paediatric patients with chronic diseases for whom treatment was introduced or modified during hospitalisation or hospital consultations. MAIN OUTCOME MEASURES: The incidence of drug-related problems (DRPs), the number and type of pharmacist intervention and paediatrician acceptance rates were assessed. Parents' understanding and drug-related needs were compared before and after medication review. Time to outpatient treatment and patient satisfaction were determined. Statistical analyses were performed in Excel. RESULTS: In total, 195 paediatric patients were included. Pharmacists identified 65 interventions, 95% of which were accepted. The most frequent DRPs included inappropriate drug administration (32.3%), herb-drug interactions (24.6%) and dose selection (17%). Parents' knowledge increased by 28% from baseline after pharmacist's medication counselling. Parents' drug-related needs concerning administration and side effects decreased by 67% and 49%, respectively, following the pharmacist's medication counselling. Most (75%) of the patients were able to get their treatment immediately after discharge. CONCLUSION: Clinical pharmacists can improve medication safety for children during the discharge process or consultations, by reducing prescription errors, optimising administration, counselling patients or parents and helping to ensure care continuity.

Effects of long-acting bronchodilators on cardiac autonomic control in COPD.

INTRODUCTION: Several studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting ß2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved. METHODS: We performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial - NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a predictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test). RESULTS: 34 patients attended four visits to receive either tiotropium 18µg, glycopyrronium 44µg, indacaterol 150 µg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate compared to placebo. No significant differences were observed for HRV and BRS between active drugs and placebo in supine position or after passive rising. CONCLUSION: We did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.

Bictegravir/emtricitabine/tenofovir alafenamide combination in the management of kidney transplant patients with HIV receiving immunosuppressants.

We report here a drug-drug interaction with tacrolimus in a HIV-positive patient with renal transplant, after switch from highly active antiretroviral therapy with boosted protease inhibitors to the combination bictegravir/emtricitabine/tenofovir alafenamide. Although the tacrolimus doses were adapted to take account of the pharmacokinetic interactions with protease inhibitors, a tacrolimus overdosage occurred in the patient nonetheless. Through this case report, we highlight the need to consider a sufficient timeframe of withdrawal of protease inhibitors, which induce a prolonged drug-drug interaction with tacrolimus. To conclude, we purport that the combination bictegravir/emtricitabine/tenofovir alafenamide could be an attractive alternative in the context of transplantation provided a discontinuation of boosted protease inhibitors for more than 48 hours before introducing tacrolimus.

Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.

INTRODUCTION: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. METHODS AND ANALYSIS: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

ß-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study.

PURPOSE: We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient ß-lactam concentrations. METHODS: In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. RESULTS: Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient ß-lactam concentrations. CONCLUSION: Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient ß-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. TRIAL REGISTRATION: NCT02820987.

A Phase II Study Evaluating the Interest to Combine UCPVax, a Telomerase CD4 TH1-Inducer Cancer Vaccine, and Atezolizumab for the Treatment of HPV Positive Cancers: VolATIL Study.

Background: There is a strong rational of using anti-programmed cell death protein-1 and its ligand (anti-PD-1/L1) antibodies in human papillomavirus (HPV)-induced cancers. However, anti-PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti-PD-1/L1 is therefore of interest. Combining anti-PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non-small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers. Methods: Patients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously. Discussion: Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti-PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT03946358.

ATMP Environmental Exposure Assessment in European Healthcare Settings: A Systematic Review of the Literature.

Since 2007, a new class of biologic products for human use called "advanced therapy medicinal products (ATMP)" have been legally integrated in the European Medical Agency. They consist of recombinant nucleic acid, engineered cells, cells, or tissues. In the United States, ATMP fall under the regulatory framework of biological products and the term "cell and gene therapy product" is used in the legislative and regulatory documents. Potential clinical applications are broad, particularly, in the field of cancer, inherited genetic disease, and regenerative medicine. Indeed, the benefit conferred by CD19 chimeric antigen receptor T cells led to the first engineered cell therapy products to be approved by the Food and Drug Administration (FDA) in 2017. Gene therapy products to treat orphan diseases are also extensively developed with many clinical trials ongoing in the world. Nevertheless, the use of these therapeutic products is complex and requires careful considerations in the terms of regulatory and hospital setting requirements, such as storage, handling, administration, and disposal which justify the implementation of a secured medication circuit. Through this systematic review of the literature, the authors wanted to compile data on the assessment of environmental exposure related to the use of ATMP in healthcare setting to secure their medication circuit. A literature search was conducted on PubMed and Web of Science, and 32 publications dealing with environmental exposure assessment and ATMP were selected. In addition, marketed ATMPs were identified and data regarding the environmental concerns were extracted from product information sections from European Public Assessment Reports (EPAR). The environmental contamination assessments were mainly addressed in the reviews rather than in original articles related to the use of ATMP. Most of the product information sections from EPAR suggested precautions rather than requirements when dealing with environmental consideration following ATMP handling. Nevertheless, these precautions usually remain elusive especially concerning waste disposal and the detection of biological material on the work surfaces, and mainly relate to the genetically modified organisms (GMO) over non-GMO cellular products. Pharmaceutical oversight and adherence to the good preparation practices and good clinical practices are essential to ensure the safe use in term of environmental concern of these new therapeutic products in healthcare setting.

COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity.

Adaptive Immune responses generated by SARS-CoV-2 virus in convalescent patients according to disease severity remain poorly characterized. To this end, we designed a prospective study (NCT04365322) that included 60 COVID-19 convalescent patients (1-month post infection) in two cohorts respectively entitled mild illness and severe pneumonia. The monitoring of peripheral immune responses was performed using IFNᵧ ELISpot assay. The serology index of each patient was investigated at the same time. Patients with severe pneumonia were older and had more comorbidities than patients with mild illness. T-cell responses in term of frequency and intensity were clearly distinct between mild illness and severe pneumonia patients. Furthermore, our results demonstrated that recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses (Cytomegalovirus, Epstein-Barr-virus and Flu-virus). The presence of potent adaptive immunity even in patients who underwent severe pneumonia sustain the rationale for the development of protective therapeutics against SARS-CoV-2.

Interaction between phytotherapy and oral anticancer agents: prospective study and literature review.

Cancer is becoming more prevalent in elderly patient. Due to polypharmacy, older adults with cancer are predisposed to drug-drug interactions. There is also an increasing interest in the use of complementary and alternative medicine (CAM). Thirty to seventy percent of patients with cancer have used CAM. Through pharmaceutical counseling sessions, we can provide advices on herb-drug interactions (HDI). All the patients seen in pharmaceutical counseling sessions were prospectively included. Information was collected during these sessions: prescribed medication (oral anticancer agents (OAA) and other drugs), CAM (phytotherapy especially), and use of over-the-counter (OTC) drugs. If pharmacist considered an interaction or an intervention clinically relevant, the oncologist was notified. Then, a literature review was realized to identify the potential HDI (no interactions, precautions for use, contraindication). Among 201 pharmacist counseling sessions, it resulted in 104 interventions related to 46 HDI, 28 drug-drug interactions and 30 others (wrong dosage, omission…). To determine HDI, we review 73 medicinal plants which are used by our patients with cancer and 31 OAA. A total of 1829 recommendations were formulated about 59 (75%) medical plants and their interaction with an OAA. Herb-drug interactions should not be ignored by healthcare providers in their management of cancer patients in daily practice.

Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.