Impact of the COVID-19 outbreak on the reporting of adverse drug reactions associated with self-medication.

OBJECTIVES: The primary objective of the present study was to describe the characteristics of adverse drug reactions (ADRs) linked to self-medication that were notified to the French Pharmacovigilance Database (FPVD) during the COVID-19 outbreak in 2020 first wave. The secondary objective was to compare the characteristics of these ADRs in 2020 with those notified during the same calendar period a year previously. MATERIAL AND METHODS: We analyzed ADRs recorded in the FPVD between March 15th and May 31st, 2020 vs. the same dates in 2019. Only ADRs linked to self-medication were analyzed. Descriptive statistics were used to obtain an overview of the types and characteristics of these ADRs. RESULTS: Of 3114 ADRs notified to the FPVD during the COVID-19 period in 2020, 114 (3.7%) were linked to self-medication. The equivalent proportion in 2019 was 1.6% (113 out of 7097). Half of the ADRs notified in 2020 were "serious". The median age of affected patients was 30.5, and 22% of the ADRs concerned children. Of the 114 ADRs linked to self-medication, 107 (66%) were for prescription-only drugs. The three mostly frequently suspected ATC classes were analgesics, psycholeptics, and antibacterials for systemic use. The most frequent ADRs were general disorders, gastrointestinal disorders, and nervous system disorders. The main difference between the non-COVID-19 period and the COVID-19 period was the higher proportion of medication errors during the latter. CONCLUSION: The present study is the first to have reported on ADRs linked to self-medication and notified during a COVID-19 outbreak. Further studies of self-medication patterns and their consequences in a pandemic context are mandatory and effective information on medication use (including self-medication and its dangers) during a pandemic is essential.

Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012.

BACKGROUND: Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000-2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period. METHODS: The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium. RESULTS: A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re-increased after 2006. Male patients were more frequent in the subgroup "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure. CONCLUSION: Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences.

Severe neurological disorders and refractory aspergillosis in an adolescent treated by vincristine and voriconazole.

WHAT IS KNOWN AND OBJECTIVE: Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. CASE DESCRIPTION: We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains. It shows the high variability of the trough serum concentration of voriconazole leading to antifungal treatment failure and suggests that its own central neurotoxicity could also be potentiated by vincristine. WHAT IS NEW AND CONCLUSION: Given the risk of either insufficient antifungal efficacy or excessive neurological disorders, this case warns on a probable unfavourable risk-benefit profile of voriconazole during vincristine-based chemotherapy in adolescents.

Neonatal leg fracture and constriction ring syndrome: A case report and literature review.

Congenital constriction of the limbs is usually due to amniotic band syndrome, which often causes damage to the skin and soft tissues. We report an unusual case in which a neonate had recent fractures of both leg bones with an amniotic band encircling the limb. Non-operative treatment was successful. Challenges to the management of neonatal limb constriction include the absence of a consensus about the best treatment and the high frequency of damage to vessels and nerves.

Functional characterisation of an intron retaining K(+) transporter of barley reveals intron-mediated alternate splicing.

Intron retention in transcripts and the presence of 5' and 3' splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K(+) transporter, HvHKT2;1, with stably retained introns from barley (Hordeum vulgare) in yeast (Saccharomyces cerevisiae), and transcript profiling in yeast and transgenic tobacco (Nicotiana tabacum) is presented. Expression of intron-retaining HvHKT2;1 cDNA (HvHKT2;1-i) in trk1, trk2 yeast strain defective in K(+) uptake restored growth in medium containing hygromycin in the presence of different concentrations of K(+) and mediated hypersensitivity to Na(+) . HvHKT2;1-i produces multiple transcripts via alternate splicing of two regular introns and three exons in different compositions. HKT isoforms with retained introns and exon skipping variants were detected in relative expression analysis of (i) HvHKT2;1-i in barley under native conditions, (ii) in transgenic tobacco plants constitutively expressing HvHKT2;1-i, and (iii) in trk1, trk2 yeast expressing HvHKT2;1-i under control of an inducible promoter. Mixed proportions of three HKT transcripts: HvHKT2;1-e (first exon region), HvHKT2;1-i1 (first intron) and HvHKT2;1-i2 (second intron) were observed. The variation in transcript accumulation in response to changing K(+) and Na(+) concentrations was observed in both heterologous and plant systems. These findings suggest a link between intron-retaining transcripts and different splice variants to ion homeostasis, and their possible role in salt stress.

[Pulmonary function in children after neonatal meconium aspiration syndrome]. / Fonction respiratoire des enfants ayant des antécédents d'inhalation méconiale.

BACKGROUND: Meconium aspiration syndrome is a disease of the newborn mature or post mature. The acute pulmonary consequences can be extremely severe. In the few studies of the long-term pulmonary sequelae, it seems that certain children surviving meconium aspiration syndrome keep an obstructive syndrome. The aim of our study was to assess long term respiratory residual damage from meconium aspiration syndrome. METHODS: During a seven-year period going from 1994 to 2000, we reviewed the files of children hospitalized in neonatology department of Sfax for meconium aspiration syndrome. The children who were convoked (group M: n=27), underwent spirometry, followed by an exercise stress. An age matched control group (group C: n=23) of healthy children was investigated in the same way. RESULTS: The group M comprised 15 boys and 12 girls aged four to 11, an average of 7+/-1.9 years. With the study of the respiratory function, we did not find an obstructive syndrome. Spirometry revealed a total pulmonary capacity in an average of 133+/-55.65% of theoretical (group M) versus 105.5+/-27.96% of theoretical (group C) (P<0,01), testifying to alveolar hyperinflation. Spirometry fulfilled 5, 10 and 15 min after exercise showed a FEV1 reduction of respectively 8.5 versus 2 (P<0.05); 9.5 versus 3 (P<0.01) and 10.5 versus 4 (P<0.05). CONCLUSION: Children surviving meconium aspiration syndrome tend to develop alveolar hyperinflation and airway hyperreactivity to exercise.

Parkinsonism and/or cognitive impairment with valproic acid therapy: a report of ten cases.

BACKGROUND: Valproic acid (VPA) is commonly prescribed and is generally considered to have a good safety profile. Severe neurological side effects, such as acute encephalopathy or tremor, are well-known. Parkinsonian syndromes and cognitive impairment have been very rarely reported with this drug. METHODS: Ten cases of reversible parkinsonism associated with VPA in 6 women and 4 men, associated with marked cognitive impairment in six cases, are described. These side effects sometimes occurred after several years of good tolerability. RESULTS: All patients had serum levels within the therapeutic range (50-100 microg/ml). Symptoms improved several weeks or months after discontinuation of VPA therapy in every case. CONCLUSIONS: Several cases of parkinsonian syndromes have been reported in the literature, but usually in children or young adults. These symptoms had an insidious and progressive onset. Clinical features can mimic Parkinson's disease and may be confusing, especially when they occur in older patients. The mechanism of these disorders is currently unknown, but several hypotheses have been proposed. Despite the good safety of VPA therapy for several years, a drug-induced mechanism of parkinsonism or cognitive impairment must be considered in all patients treated with VPA, as discontinuation of the drug can induce significant improvement of the patient's neurological and mental status.

[Extrapyramidal adverse effects of veralipride (Agreal), a drug used to treat hot flushes: a propos of 17 cases]. / Troubles extrapyramidaux sous véralipride (Agréal), traitement symptomatique des bouffées de chaleur: à propos de 17 cas.

PURPOSE: Extrapyramidal disorders associated with veralipride therapy are rarely reported and often due to a drug misuse. METHODS: We evaluated cases of extrapyramidal disorders associated with veralipride. Cases were extracted from the regional pharmacovigilance centre of Amiens database. From January 1, 1995 to September 30, 2004, cases were selected on the basis of the occurrence of extrapyramidal disorders under veralipride therapy. RESULTS: Seventeen cases of veralipride-induced extrapyramidal disorders were found. They consist of 16 menopausal women and one old man with LH-RH antagonist-induced hot flushes. Mean age was 61 years (48-73). Adverse effects were acute dyskinesia (n=2) or parkinsonian syndrome, which occurred after several months or years of treatment (n=15). Parkinsonism was associated with other extrapyramidal symptoms in 8 cases: tardive dyskinesia (n=6), postural tremor (n=3), myoclonia (n=1), and trunk dystonia (n=1). In all cases, outcome was favorable after drug discontinuation. In most cases the tablet-free interval was not respected: this may lead to prolonged striatal D2 receptors blockade. It must be added that the diagnosis was often delayed and patients were considered as suffering from idiopathic Parkinson's disease. CONCLUSIONS: Prescribers should be aware that veralipride is a neuroleptic and could induce potentially severe extrapyramidal disorders. Increase veralipride prescription is expected due to the recent restriction of hormonal replacement therapy for menopause. The physicians should also use veralipride according to the Summary of the Product Characteristics.

Acute aphasia in multiple sclerosis: A multicenter study of 22 patients.

Aphasia is usually considered to be rare in multiple sclerosis (MS). To determine the clinical and radiologic characteristics of MS patients with acute aphasia, the authors investigated data from 2,700 patients from three MS centers and found 22 patients with acute aphasia (0.81%). Aphasia was the first clinical manifestation of MS in eight patients (36%). Brain MRI showed giant plaques in eight cases (40%). A full recovery was observed in 14 patients (64%). Furthermore, acute aphasia did not appear to be a criterion for poor prognosis.

[Value of maximum expiratory volume per second and peak expiratory flow monitoring in asthma. 77 patients]. / Intérêt du monitoring du volume expiratoire maximum par seconde et du débit expiratoire de pointe dans l'asthme. A propos de 77 patients.

A retrospective study was conducted on a sample of 77 subjects to assess the interest of computerized flowmeter "one-flow" in the diagnosis and follow up of asthma. 77 patients and a control group matched for age and sex, measured four times by day, the forced expiratory volume in one second as well as the peak expiratory flow during 15 to 30 days. The monitoring of these two variables allowed to participate to the exclusion from the study of fifteen patients whose asthma diagnosis was informed. It also allowed the confirmation of four occupational asthma. Concerning the adherence of the treatment by patients, the conclusion of the study showed that 47% of patients modified their treatment at home without consulting their doctors, 38% resorted to their doctor and only 3% resorted to the emergencies.

[Dementia and extrapyramidal problems caused by long-term valproic acid]. / Démence et troubles extra-pyramidaux sous acide valproïque au long cours.

Among the side-effects attributed to valproic acid (VPA), the occurrence of Parkinsonian syndromes and cognitive impairment is very uncommonly reported. We describe five cases of reversible associated Parkinsonism. These cases were observed in epileptic patients, 57 to 74 years old, two women and three men. Extrapyramidal disorders appeared after various durations of treatment (from 6 months to 10 years). Dementia characterized by an insidious onset was associated in three cases and bradypsychia in one case. Brain pseudoatrophy was present in three patients. In all cases the signs and symptoms improved some weeks or months after discontinuation of VPA. In the literature some cases, usually in young adults or children, have been reported. In a prospective study, Armon et al. found various abnormal symptoms and signs related to motor and cognitive function impairment in patients with long-term VPA therapy. These side-effects may be related to a disturbance in the gabaergic pathways in the basal ganglia system. It is of interest to consider that delta 2-valproic acid, a metabolite of VPA, is especially accumulated in selected areas of the brain: the substantia nigra, superior and inferior colliculus, hippocampus and medulla.

Changes in Fos-like immunoreactivity evoked by maturation of the sneeze reflex triggered by nasal air puff stimulation in kittens.

The sneeze reflex is a valuable tool for exploring the maturation of the respiratory control in the newborn as it alters both inspiratory and expiratory activities. Air puff stimulation of the superior nasal meatus innervated by ethmoidal afferents consistently evokes sneeze in adult cats. Such stimulation evokes only a reinforcement of expiratory activities in newborn kittens. This study demonstrates that the pattern of Fos-like immunoreactivity evoked by nasal stimulation changes during functional maturation of sneeze. Nasal stimulation evoked immunoreactivity (i) in the trigeminal sensory complex, at the levels where nasal afferents project, (ii) in the reticular formation, (iii) in the solitary complex and (iv) in the parabrachial area of mature kittens. The evoked immunoreactivity was the same in newborn kittens as in mature kittens in the projection areas of the nasal primary afferents. Fos response was less than half that in mature kittens in the reticular formation and absent in the solitary complex or the parabrachial area. Sneeze can be elicited from the time when evoked immunoreactivity in the solitary complex and the parabrachial area is above control levels. These data provide evidence that the maturation of sneeze is dependent on the development of central relays allowing peripheral inputs to be integrated by neurons engaged in respiratory control.