Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders.

INTRODUCTION: The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. METHODS: For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. RESULTS: The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. CONCLUSIONS: Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder.

Long-Acting Injectable Antipsychotic Treatment during Pregnancy: A Case Series.

INTRODUCTION: Data from the literature show that prolonged-release injectable antipsychotics (LAIs) ensure constant blood drug levels better patient compliance and offer a simpler treatment regimen for both patients and caregivers. This observational-descriptive study aims to detect the possible complications found in newborns of women with bipolar or psychotic disorders and LAI therapy during pregnancy. METHODS: This study involved women with psychotic disorders during pregnancy who contacted the Teratology Information Center of Bergamo, Italy between 2016 and 2021 to receive counseling on the possible risks of exposure to LAI therapy. The follow-up procedure was carried out by telephone interview or direct contact with the patient and/or her physician. RESULTS: In this study, LAI treatment in pregnancy was not associated with an increased risk of malformations. All but one of the children in the sample were born healthy and the mothers maintained psychopathological compensation during pregnancy. CONCLUSIONS: This study showed that, despite the small size of the sample under examination, the administration of LAIs do not compromise the normal intrauterine development of the unborn child and there were no evident major malformations.

Dexrazoxane for rapid extended livedo reticularis-like skin reaction due to systemic epirubicin diffusion during transcatheter arterial chemoembolization procedure for hepatocellular carcinoma.

Skin reactions after transarterial chemoembolization (TACE) with anthracyclines are rare and mostly limited to small areas. We describe a 56-year-old male with hepatocellular carcinoma treated with epirubicin chemoembolization. Immediately the procedure, pain on the right side and an extended livedo reticularis-like skin reaction appeared. Since dexrazoxane, a topoisomerase-II catalytic-cycle inhibitor, has been shown to be effective in preventing or reducing skin necrosis and ulceration following anthracycline extravasation, the drug was administered 8 h after TACE and repeated in the following 2 days. Due to marked extrahepatic diffusion of epirubicin as evidenced by computed tomography imaging, the patient showed signs of systemic organ involvement. The critically ill patient required close follow-up and intensified treatment including blood supply and pulmonary drainage of a pleural effusion. The patient presented a significant clinical improvement of the skin lesions and resolution of organ involvement with normalization of laboratory parameters after dexrazoxane. In conclusion, adverse extended skin reactions and severe systemic effects related to anthracyclines diffusion could be properly treated with dexrazoxane infusion.

Open issues in management of carbon monoxide poisoning in pregnancy: practical suggestions.

Carbon monoxide (CO) poisoning during pregnancy may cause deleterious effects to the fetus. Hyperbaric oxygen therapy (HBO) in pregnancy is proven to be safe and it is considered to be beneficial, reducing the severity of the fetal injuries. However, a number of issues are still to be discussed, among them the question of the carboxyhemoglobin (COHb) levels that trigger HBO therapy in pregnant CO poisoned patients. In this letter we report some practical suggestions for organizations wishing to develop their own protocols.

Medications prescriptions in COVID-19 pregnant and lactating women: the Bergamo Teratology Information Service experience during COVID-19 outbreak in Italy.

Objectives The severe acute respiratory syndrome coronavirus 2 (COVID-19) outbreak in Italy, especially in Lombardy and Bergamo city, represented probably nowadays one of the first major clusters of COVID-19 in the world. The aim of this report is to describe the activity of Bergamo Teratology Information Service (TIS) in supporting the public and health-care personnel in case of drug prescriptions in suspected/confirmed COVID-19 pregnant and lactating patients during COVID-19 outbreak in Italy. Methods All Bergamo TIS requests concerning COVID-19 pregnant and lactating women have been retrospectively evaluated from 1 March to 15 April 2020. Type of medications, drug's safety profile and compatibility with pregnancy and lactation are reported. Results Our service received information calls concerning 48 (9 pregnant, 35 lactating) patients. Among pregnant and lactating women, the requests of information were related to 16 and 60 drugs prescriptions respectively. More than half concerned drugs prescriptions during the first and second trimester (13/16) and during the first six months of lactation (37/60). Hydroxychloroquine and azithromycin were the most involved. Conclusions Hydroxychloroquine and azithromycin at dosages used for COVID-19 may be considered compatible and reasonably safe either in pregnancy and lactation. Antivirals may be considered acceptable in pregnancy. During lactation lopinavir and ritonavir probably exhibit some supportive data from literature that darunavir and cobicistat do not. Tocilizumab may be considered for COVID-19 treatment because no increased malformation rate were observed until now. However caution may be advised because human data are limited and the potential risk of embryo-fetal toxicity cannot be excluded.

Lacosamide-induced recurrent ventricular fibrillation: A case report.

Lacosamide, a new antiepileptic drug, acts at central nervous system level but may also affect the heart, increasing the risk of cardiac arrhythmias. Only few cases of lacosamide-induced cardiac dysrhythmia have been published. We report a case of several episodes of a life-threatening ventricular fibrillation requiring cardioversion following the first doses of lacosamide as adjunctive epilepsy treatment.

Clozapine-induced anemia: A case-report
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Clozapine, an atypical antipsychotic, can cause potentially life-threating side effects such as agranulocytosis. Our case presents a picture of severe anemia without any depression of the white cells or platelet lines. A 36-year-old man with treatment-resistant schizophrenia was admitted to the Psychiatric Unit for therapy assessment. After admission, he was gradually switched to clozapine treatment, 400 mg/d. General laboratory test results were normal, with a hemoglobin (Hb) level of 15.2 g/dL. The Hb level gradually decreased to 7.1 g/dL 10 weeks after switching to clozapine, when the patient underwent blood transfusion and clozapine therapy was stopped. No evidence of bleeding was noted. The reticulocyte count was less than 60.000/µL. Other anemia causes were excluded. Bone marrow aspiration performed at 10 weeks revealed red cell hypocellularity, while myelopoietic and megakaryocytic cell lines were normal. All these findings confirmed the diagnosis of pure red cell aplasia. The Hb level gradually increased to 13.3 g/dL 4 weeks after clozapine discontinuation, and the patient was discharged with olanzapine 5 mg/d. Clozapine has been reported to cause hematological abnormalities. In our patient, the diagnosis of pure red cell aplasia was made on the basis of severe and selective anemia, reticulocytopenia, and erythroid aplasia. The pathogenesis of hematologic abnormalities due to clozapine treatment is not known. Suggested mechanisms include a direct toxic effect of clozapine, or its metabolite, on the erythroid precursor cells, or formation of a drug-antibody complex. These aspects call for further and deeper research and reports of clinical observations.

Neonatal toxicity following maternal citalopram treatment.

Late gestational exposure to citalopram, may be associated with a neonatal toxicity syndrome with immediate onset at birth or soon after birth and sometimes may be mistaken for neonatal withdrawal syndrome. A 3860 g infant was delivered at 40 weeks gestation. The mother had been taking citalopram 20 mg/day until the day of delivery. Fifteen minutes after birth, the baby became hypertonic. Neonatal serotonin toxicity due to citalopram seems the most likely mechanism, though an important differential diagnosis is a citalopram withdrawal syndrome. We suggest the hypothesis that neonatal withdrawal syndrome may follow citalopram serotonin toxicity.

Screen complexity of Italian institutional cancer web sites.

The discordant results of a comparison between calculated and perceived screen complexity of 14 Italian Institutional Cancer Web Sites are described here.

Usability of institutional cancer web sites: an Italian case study.

In order to evaluate if and to what extent Italian speaking cancer patients can benefit from information available on cancer web sites, an "in vitro" usability (ISO definition) study has been carried out. It investigated the usability of the web sites of the most representative Italian Institutions in the oncological field for the adult patients needing to find information about head and neck cancer. Specific evaluation criteria from the literature were used. The results point out some problems about accessibility, in line with other studies, and about the usefulness of the contents, in particular in the web sites of care delivery institutions: a grey present situation, but there are already grounds for significant improvement. Institutions and organizations must not waste the opportunity of being valuable sources in order to build the so called "informed patient," and the usability of their web sites could make the difference.

[Antidotes availability in Emergency Departments of the Italian National Health System and development of a national data-bank on antidotes]. / Disponibilità di antidoti nei servizi d'urgenza del Sistema Sanitario Nazionale e realizzazione della Banca Dati Nazionale degli Antidoti (BaNdA).

The availability of antidotes in Italian hospitals has been evaluated through the answers to a specific questionnaire sent to all Italian Emergency Departments, Intensive Care Units, 118 emergency response system, and Poison Centres. Five Poison Centres and, approximately, the 30% of the Emergency Departments and Intensive Care Units of all Italian emergency hospitals answered to the questionnaire. The results point out an insufficient availability of antidotes in the Italian emergency hospitals, with an almost total absence of those necessary for the treatment of less frequent and less known poisonings (e.g. digoxin, industrial agents), also when the antidote is a lifesaving drug. To improve the antidotes availability for the toxicological emergencies and to facilitate its supplying, a "national antidotes data-base" (BaNdA) has been realized, freely available to the hospital services which register themselves and make their antidotes stockpile available.

Diagnostic accuracy of urinary amanitin in suspected mushroom poisoning: a pilot study.

BACKGROUND: Amatoxin-containing species are responsible for the most severe cases of mushroom poisoning, with high mortality rate. Therefore, this poisoning should be ruled out in all patients presenting gastrointestinal symptoms after wild mushroom ingestion. OBJECTIVE: To determine sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficacy (DE) of urinary amanitin analysis in cases of suspected mushroom poisoning. METHODS: All cases of mushroom ingestion referred to a Poison Center during a one-month period were analyzed. Amanitin measurements were performed by ELISA method (functional least detectable dose 1.5 ng/ml; cut-off value not clearly established). Gastrointestinal symptoms latency and initial clinical assessment were considered alternative diagnostic tools. Definitive diagnosis was used as the reference standard. RESULTS: Among 61 patients included in the study, amatoxin poisoning was diagnosed in 10 cases. Urine samples were collected 5.5 to 92 hours after mushroom ingestion. Urinary amanitin DE was 91.8%, 93.4%, and 80.3%, based on the cut-off value considered (1.5, 5.0, and 10.0 ng/ml, respectively). Symptoms latency longer than 6 hours and initial clinical assessment DE were 70.5% and 67.2%, respectively. To identify amatoxin poisoning, initial clinical assessment resulted more sensitive and urinary amanitin analysis more specific. CONCLUSIONS: Urinary amanitin analysis is a valuable diagnostic tool and may significantly contribute to the management of suspected mushroom poisoning. At present, the best diagnostic accuracy can be obtained taking advantage of both the high sensitivity and negative predictive value of the clinical assessment performed by an experienced toxicologist, and the high specificity and positive predictive value that characterize urinary amanitin analysis.

[Exotic snakes in Europe. A case of Mexican Moccasin (Agkistrodon bilineatus) snakebite]. / Serpents exotiques en Europe. Un cas de morsure par Mocassin du Mexique (Agkistrodon bilineatus).

INTRODUCTION: In the last years exotic snakebite envenomations are increasingly reported. These cases are difficult to manage because of the limited experience of European physicians in the treatment of bites from such venomous snakes; moreover, specific antivenoms are unevenly stocked and they are difficult to find in case of a medical emergency. OBSERVATION: A 39-year-old herpetologist was bitten in his right hand by a mexican moccasin (Agkistrodon bilineatus) at the workplace, and presented in the Emergency Department 19 hours later. At admission, clinical evaluation showed local necrosis, swelling involving the entire limb up to the trunk, and severe pain. The specific antidote, not stocked in Italy, was sought abroad; its finding and routeing up to spot delivery required 12 hours. The antivenom, given 32 hours after the bite with no adverse reactions, was only partially effective. The clinical course was characterized by extensive edema with rhabdomyolysis. The necrotic wound at the bite site required after several days surgical debridement, and eventually skin graft. At 3 months follow-up, motor impairment of his right hand fingers with functional disability was still present. COMMENTS: The envenomation by Agkistrodon bilineatus has some clinical aspects in common with that by European viper species, although crotalid venom usually causes more severe manifestations. The antivenom supply from a foreign country may delay its administration. A specific legislation aimed to simplify antidotes importing procedures for professional snake handlers may improve antivenoms availability and allow their timely use, as soon as clinically indicated.

Cardiovascular glycoside-like intoxication following ingestion of Thevetia nereifolia/peruviana seeds: a case report.

Some plants contain glycoside compounds which determine cardiovascular symptoms similar to those observed after acute toxic digoxin administration. The present case report involves a patient who showed important cardiovascular symptoms following the ingestion of Thevetia nereifolia/peruviana seeds. About 30 min after ingestion, a 65-year-old man presented with dizziness, giddiness, numbness and a burning sensation, diarrhea, sweating, vomiting and ECG changes. At the time of admission he presented with tremors; his body temperature was 37 degrees C, and blood analysis gave the following results: K 5.6 mEq/l, myoglobin 176 IU, troponin T 0.10 ng/ml, PO2 69 mmHg, PCO2 37.4 mmHg, pH 7.33, HCO3- 19.9 mEq/l, hemoglobin 14.8 g/dl, saturation 92.5%. Echocardiography showed a left ventricle with normal global and segmentary contractility. The following days, the patient showed a reduction, until total resolution, of the atrioventricular block and of the alterations of the ST segment. The ectopic beats also resolved; K value before discharge was 4.4 mEq/l. On the third day, the serum levels of digoxin were 0.15 ng/ml. This case report is important because it describes all the cardiovascular and non-cardiovascular signs of glycoside toxicity in an adult patient who accidentally swallowed only two seeds (non-fatal dose) of Thevetia.