Neuropsychiatric Effects of Antiviral Drugs.

The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been published regarding the central nervous system toxicity of antiviral agents. They may cause significant neuropsychiatric complications, which range from mild symptoms such as irritability and difficulty sleeping to severe complications such as depression, psychosis, and painful peripheral neuropathy, side effects which may necessitate discontinuation of treatment. The pathogenetic mechanisms may involve molecular targets common to other centrally active drugs, including human monoamine oxidase-A (MAO-A), serotonin receptors, gamma-aminobutyric acid (GABA) GABA-A receptors, 5-HT2A and 5-HT2C receptors and others. Notable examples include oseltamivir which may act as MAO inhibitor and efavirenz, which has an affinity for serotonin 5-HT2 and GABA-A receptors, the serotonin transporter, the MAO enzyme, and the vesicular monoamine transporter, with subjective effects which may be similar to those of the psychedelic hallucinogen lysergic acid diethylamide (LSD). Other antiviral drugs with prominent nervous system effects include nucleoside reverse transcriptase inhibitors, which are associated with the development of peripheral neuropathy after prolonged use (an effect strongly associated with older drugs which have since fallen into disfavor such as stavudine) and interferons, which may cause depression. Clinicians should be familiar with such adverse effects in order to recognise them promptly once they occur and manage them appropriately.

Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain.

Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.

Intubation and mechanical ventilation of patients with COVID-19: what should we tell them?

Severe COVID-19 illness is characterised by the development of Acute Respiratory Distress Syndrome (ARDS), for which the mainstay of treatment is represented by mechanical ventilation. Mortality associated with ARDS due to other causes is in the range of 40-60%, but currently available data are not yet sufficient to draw safe conclusions on the prognosis of COVID-19 patients who require mechanical ventilation. Based on data from cohorts of the related coronavirus-associated illnesses, that is to say Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), prognosis would seem to be worse than ARDS due to other causes such as trauma and other infections. Discussion of prognosis is central to obtaining informed consent for intubation, but in the absence of definitive data it is not clear exactly what this discussion should entail.

Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome.

OBJECTIVE: The polycystic ovary syndrome (PCOS) is a common and complex disease with unclear pattern of inheritance, characterized by an androgen excess, while hyperinsulinemia and insulin resistance (IR) are common features of the syndrome. The angiotensin I converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism was proved to be involved in many pathophysiological conditions, including hypertension and IR. DESIGN: The purpose of this study was to evaluate the involvement of the ACE gene polymorphism in the pathogenesis of PCOS. METHODS: In a case-control association study involving 801 PCOS women and 266 healthy controls, hormonal determinations and ACE polymorphism genotyping were performed. The PCOS women were classified into three groups: Group A presented biochemical hyperandrogenism, combined with anovulation and polycystic ovarian morphology; Group B, clinical hyperandrogenism combined with anovulation and polycystic ovarian morphology; and Group C, chronic anovulation and polycystic ovarian morphology. RESULTS: A significant increase in the frequency of the DI genotype of the ACE polymorphism was detected in PCOS women as a whole (P=0.035), in PCOS Group A (P=0.039) and Group B (P=0.010), while there was no difference in Group C (P=0.939). Significant difference was also observed in hyperandrogenic PCOS women as a whole (Group A+B) (P=0.017). The II genotype was positively correlated with HOMA-IR and QUICKI and with fasting insulin and glucose/insulin ratio in these groups. CONCLUSIONS: The association study of the ACE I/D polymorphism in PCOS women demonstrates an increase in the DI genotype incidence and an association of the II genotype with IR.

Increased plasma viscosity in young women with polycystic ovary syndrome using an oral contraceptive containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate.

OBJECTIVES: To investigate the influence of 6 months of treatment with an oral contraceptive (OC) containing 35 µ g ethinyl estradiol and 2 mg cyproterone acetate on plasma viscosity (PV) in young women with polycystic ovary syndrome (PCOS). DESIGN: Patients with PCOS were assessed for PV before and after 6 months of treatment with an OC containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate. PV was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C. SETTINGS: Subjects were recruited from the Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology at the University Hospital of Patras, Greece. PATIENTS: The study included 66 young women with PCOS. MAIN OUTCOME MEASURES: PV. RESULTS: In PCOS women as a whole, PV at baseline was 1.249 ± 0.049 mm(2)/s (n = 66). After 6 months of treatment with an OC containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate, PV was increased to 1.268 ± 0.065 mm(2)/s (p = 0.038). The difference between PV before and after 6 months of treatment with an OC containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate (Δviscosity) was 0.01864 ± 0.071452 mm(2)/s. ΔViscosity was related to ?fibrinogen (r = 0.270, p = 0.046), to Δhematocrit (r = 0.514, p = 0.09) and to Δtriglycerides (r = 0.292, p = 0.021). CONCLUSION: Young women with PCOS presented an increased PV under OC treatment with 35 µg ethinyl estradiol and 2 mg cyproterone acetate.

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia.

PURPOSE: The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. METHODS: The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR-restriction fragment length polymorphism (RLFP) assay. RESULTS: No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. CONCLUSION: The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.