Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France.

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

Choosing the right chronic medication for hemodialysis patients. A short ABC for the dialysis nephrologist.

BACKGROUND: Adapting drug treatments for patients on hemodialysis with multiple chronic pathologies is a complex affair. When prescribing a medication, the risk-benefit analysis usually focuses primarily on the indication of the drug class prescribed. However, the pharmacokinetics of the chosen drug should also be taken into account. The purpose of our review was to identify the drugs to be favored in each therapeutic class, according to their safety and pharmacokinetic profiles, for the most common chronic diseases in patients on chronic hemodialysis. METHODS: We conducted a narrative review of the literature using Medline and Web of Science databases, targeting studies on the most commonly-prescribed drugs for non-communicable diseases in patients on chronic hemodialysis. RESULTS: The search identified 1224 articles, 95 of which were further analyzed. The main classes of drugs included concern the cardiovascular system (anti-hypertensives, anti-arrhythmics, anti-thrombotics, hypocholesterolemics), the endocrine and metabolic pathways (anti-diabetics, gastric anti-secretory, anticoagulant, thyroid hormones, anti-gout) and psychiatric and neurological disorders (antidepressants, anxiolytics, antipsychotics and anti-epileptics). CONCLUSION: We report on the most often prescribed drugs for chronic pathologies in patients on chronic hemodialysis. Most of them require adaptation, and in some cases one better alternative stands out among the drug class. More pharmacokinetic data are needed to define the pharmacokinetics in the various dialysis techniques.

[Therapeutic plasmapheresis procedures: An alternative to the disruption of the supply of polyvalent immunoglobulin in autoimmune pathologies. Medico-economic study]. / Les techniques de plasmaphérèse thérapeutique : une alternative à la rupture d'approvisionnement en immunoglobuline polyvalente dans les pathologies auto-immunes. Étude médico-économique.

INTRODUCTION: The supply of human polyvalent immunoglobulin has been under severe pressure for several years. This has led to a prioritisation of indications and a record increase in the amount of reimbursement without solving the problem of demand. Treatment by therapeutic plasmapheresis appears to be an alternative to be considered for the treatment of certain dysimmune diseseases. To discuss this alternative, we are conducting a medico-economic study comparing the polyvalent immunoglobulin strategy versus different therapeutic plasmapheresis system in the treatment of a chronic dysimmune disease. POPULATION AND METHOD: The medico-economic study was conducted using the example of a 75 kg patient with chronic polyradiculoneuritis dependent on chronic therapy with a comparison of sequential treatment with one session of therapeutic plasmapheresis versus a course of intravenous polyvalent immunoglobulin. The medico-economic study includes an evaluation from a public health care system perspective complemented by a hospital-based approach that justifies estimating the cost of different therapeutic plasmapheresis systems based on a bottom-up micro-costing approach. RESULTS: From the point of view of the care system, for information, a 20 g bottle of polyvalent immunoglobulin has a similar cost to a therapeutic plasmapheresis session. In our example, the cost of a maintenance treatment repeated every 2 to 4 weeks in chronic polyradiculoneuritis in a 75 kg patient is 1284.13 euros for a therapeutic plasmapheresis session versus 7331.60 to 9426.84 euros for a 1.5 to 2 mg/kg polyvalent immunoglobulin treatment. Furthermore, from the point of view of the hospital system, the cost of the different TT techniques evaluated varies moderately with the cost depending mainly on the quantity of albumin infused or the medical device used. CONCLUSION: In the chronic sequential treatment of chronic polyradiculoneuritis, the cost of therapeutic plasmapheresis could be lower than with polyvalent immunoglobulin from a healthcare system perspective. The cost to the health care facility between different therapeutic plasmapheresis techniques differs little. This study provides arguments suggesting that if therapeutic plasmapheresis can be implemented with a dedicated technical platform, it is a serious alternative to be considered without additional costs.

Impact of drug reconciliation at discharge and communication between hospital and community pharmacists on drug-related problems: study protocol for a randomized controlled trial.

BACKGROUND: Patients are at risk of drug-related problems (DRPs) at transition points during hospitalization. The community pharmacist (CP) is often the first healthcare professional patients visit after discharge. CPs lack sufficient information about the patient and so they may be unable to identify problems in medications, which may lead to dispensing the wrong drugs or dosage, and/or giving wrong information. We aim to assess the impact of a complex intervention comprising of medication reconciliation performed at discharge by a hospital pharmacist (HP) with communication between the HP and CP on DRPs during the seven days following discharge. METHODS/DESIGN: The study is a cluster randomized crossover trial involving 46 care units (each unit corresponding to a cluster) in 22 French hospitals during two consecutive 14-day periods, randomly assigned as 'experimental' or 'control' (usual care) periods. We will recruit patients older than 18 years of age and visiting the same CP for at least three months. We will exclude patients with a hospital length of stay of more than 21 days, who do not return home or those in palliative care. During the experimental period, the HP will perform a medications reconciliation that will be communicated to the patient. The HP will inform the patient's CP about the patient's drug therapy (modification in home medication, acute drugs prescribed, nonprescription treatments, and/or lab results). The primary outcome will be a composite outcome of any kind of drug misuse during the seven days following discharge assessed at day seven (±2) post-discharge by a pharmacist in charge of the study who will contact both patients and CPs by phone. The secondary outcome will be unplanned hospitalizations assessed by phone contact at day 35 (±5) after discharge. We plan to recruit 1,176 patients. DISCUSSION: This study will assess the impact of a reconciliation of medications performed at patient discharge followed by communication between the HP and the patient's CP. It will allow for identifying the type of patients in France for which the intervention is most relevant. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (number: NCT02006797) on 5 December 2013.

Psychological and physiological effects of bupropion compared to methylphenidate after prolonged administration in healthy volunteers (NCT00285155).

PURPOSE: Bupropion is largely used as an antidepressant and smoking cessation therapy. The aim of this work was to compare pharmacodynamic properties of bupropion and the amphetamine-like methylphenidate after sustained administration in humans. METHODS: Twelve male volunteers completed this randomized, double-blind, placebo controlled, cross-over study. Bupropion and methylphenidate were administered separately for initial half-dose 6-day periods (150 and 10 mg respectively) followed by full-dose 8-day periods (300 and 20 mg respectively). Outcomes were subjective feelings, cognitive performances, autonomic and physiological parameters. RESULTS: Data are expressed as mean(SEM). After repeated administration, bupropion, like methylphenidate, decreased asthenia-fatigue [44(3.2) and 42(3.7), respectively vs. 53(4.1) for placebo; p = 0.034], despite an impairment of sleep onset [-4.3(3.32) and -1.9(3.76), respectively vs. +7.5(3.69); p = 0.016]. Both drugs increased resting diastolic blood pressure [67.9(1.23) and 65.7(0.98), respectively vs. 62.5(1.42) mm Hg; p = 0.001], body temperature [36.5(0.12) and 36.5(0.14) vs. 36.3(0.10) °C; p = 0.037] and decreased body weight [-0.7(0.23) and -0.6(0.22), respectively vs. +0.2(0.27) kg; p = 0.038]. No significant change could be observed on cognitive functions, appetite and energy consumption. CONCLUSION: Although it may not share all the properties of stimulant drugs, the effect profile of bupropion presents a number of similarities with that of methylphenidate over a 2-week treatment period.

Selecting healthy volunteers in specific populations: a retrospective analysis of clinical and laboratory screening.

Healthy volunteers must undergo a medical examination before enrollment in a clinical trial. An increasing number of trials include specific populations designed to match the target populations of the drugs tested. Our study aimed at evaluating which investigations are the most appropriate in different sub-populations of healthy volunteers. Data from 350 healthy volunteers who attended our Research Center from 1997 to 2004 were retrospectively analysed. Volunteers were distributed into five sub-populations: young men, senior men, overweight men, young women, postmenopausal women. The screening procedure comprised a review of medical history, physical examination, electrocardiogram and laboratory tests. Ineligibility criteria were classified as non-medical causes, protocol specific medical causes and non-specific medical causes. A total of 148 subjects (42%) were not-eligible, mainly because of non-specific medical causes (111 subjects), including abnormal medical history (34.5% of all ineligibilities). Blood pressure abnormalities were frequent in all sub-populations except young women. Electrocardiographic abnormalities led to ineligibility of only five overweight men and one menopausal woman. Abnormal laboratory tests accounted for 19.6% of ineligibilities. In senior subjects and overweight men, serologies, liver function tests and lipid profile contributed importantly to the selection process. Low red cells count was the most frequent laboratory abnormality in young women. Erythrocyte sedimentation rate, phosphocalcic metabolism and standard clotting tests led to frequent insignificant and non-contributive abnormalities. Our study confirms that a complete review of medical history is essential and determines the major part of ineligibilities. Complementary laboratory tests are always needed and may be adjusted to the population considered.

Antipsychotics-induced ischaemic colitis and gastrointestinal necrosis: a review of the French pharmacovigilance database.

PURPOSE: First- and second-generation antipsychotics commonly cause mild gastrointestinal hypomotility. Intestinal necrosis may be a consequence of such gastrointestinal perturbations. MATERIAL AND METHODS: We reviewed all the observations of ischaemic colitis and gastrointestinal necrosis notified to the French Pharmacovigilance database (FPD) between 1997 and the end of 2006. RESULTS: Thirty-eight cases of ischaemic colitis and gastrointestinal necrosis associated with antipsychotics were analysed. The average age of the patients was 42.7 +/- 14.7 years (15-77 years). The digestive complication was an intestinal necrosis in 27 cases, an ischaemic colitis in 10 cases (with perforation in three cases), and one perforation. Surgical procedure (partial or total resection of the colon and/or small intestine) was performed in 24 patients. Six patients died despite surgery. Among the whole population, the outcome was fatal in 14 patients, 13 patients recovered with sequelae, six patients fully recovered, and the outcome remained unknown in five cases.In 55.2% of the cases, the patients were treated with more than one antipsychotic medication. The most frequently involved antipsychotics were: clozapine, levomepromazine, cyamemazine, haloperidol. Associated antimuscarinic drugs (excluding antipsychotics) were found in 68.4% of patients. DISCUSSION/CONCLUSION: Intestinal necrosis associated with antipsychotics is very rare; however mortality is high, with a rapid worsening of patients towards septic shock in spite of mild clinical symptoms. It is therefore essential to monitor the patients receiving antipsychotics especially when they are prescribed concomitant medications. The occurrence of non-specific clinical symptoms such as abdominal pain associated with vomiting and/or diarrhea should draw attention.

Möbius syndrome in a neonate after mifepristone and misoprostol elective abortion failure.

OBJECTIVE: To report a case of a child born with Möbius syndrome following exposure in utero to mifepristone and misoprostol for elective abortion. CASE SUMMARY: In the seventh week of pregnancy, a woman was administered mifepristone 600 mg and, 2 days later, misoprostol 400 mug for abortion. One month later, despite significant metrorrhagia, an ultrasound examination showed ongoing gestation. At 33 weeks and 3 days of gestation, the woman gave birth to a male with left facial palsy, microretrognathia, and axial hypotonia related to Möbius syndrome. DISCUSSION: Möbius syndrome is characterized by unilateral or bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. Other cranial nerves (eg, the hypoglossal [XII]), craniofacial or orofacial anomalies, and limb malformations are often associated. The etiology of the Möbius syndrome remains largely unknown and probably involves multiple factors. The most likely etiological hypothesis is disruption of the developing vascular system, with transient ischemia (particularly in the vertebral arteries) and fetal hypoxia. A teratogenic cause of Möbius syndrome has been suggested. The critical period for the development of Möbius syndrome following teratogen exposure appears to be 5-8 weeks of gestation. To date, mifepristone alone does not appear to have induced Möbius syndrome. In contrast, oral or vaginal misoprostol administration can lead to a significant increase in Doppler-measured uterine artery resistance and may induce uterine contractions. If these occur during the critical embryonic period, they may cause flexion in the areas of the sixth and seventh cranial nerves and decreased blood flow. CONCLUSIONS: Ineffective use of mifepristone and misoprostol in the first trimester of pregnancy may be associated with a risk of Möbius syndrome, primarily due to misoprostol activity. Women with ongoing pregnancy after failed abortion with misoprostol administration should be informed of this risk.