Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients.

BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.

Factors Associated With Cysticidal Treatment Response in Extraparenchymal Neurocysticercosis.

Extraparenchymal neurocysticercosis is the most severe form of cysticercosis, and response to treatment is suboptimal. We sought to determine how demographic and clinical characteristics and albendazole sulfoxide concentrations were related to cysticidal treatment response. We conducted a longitudinal study of 31 participants with extraparenchymal vesicular parasites who received the same treatment, albendazole 30 mg/kg/day for 10 days with dexamethasone 0.4 mg/kg/day for 13 days, followed by a prednisone taper. Response to treatment was determined by parasite volumes before and 6 months after treatment. Eight participants (25.8%) had a complete treatment response, 16 (51.6%) had a treatment response > 50% but < 100%, and 7 (22.6%) had a treatment response < 50%. Complete treatment response was significantly associated with higher concentrations of albendazole sulfoxide (P = .032), younger age (P = .032), fewer cysts (P = .049) and lower pretreatment parasite volume (P = .037). Higher number of previous cysticidal treatment courses was associated with a noncomplete treatment response (P = .023). Although the large proportion of participants with less than a complete response emphasizes the need to develop more efficacious pharmacologic regimens, the association of albendazole sulfoxide concentrations with treatment response highlights the importance of optimizing existing therapeutic regimens. In addition, the association of treatment response with parasite volume emphasizes the importance of early diagnosis.

Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series.

BACKGROUND: Neurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment. CASE PRESENTATION: The clinical and radiological pictures of six Mexican patients non-respondent to cysticidal treatment are presented. CONCLUSIONS: The possible factors involved in the cysticidal non-response are discussed and hints are provided of potentially useful changes to therapeutic protocols.

Severe cysticercal meningitis: clinical and imaging characteristics.

In disease-endemic areas, severe cysticercal meningitis (SCM) is characterized by intense inflammatory cerebrospinal fluid (CSF) and negative bacterial and fungal cultures. There have been no systematic studies of SCM. We characterized patients with SCM and compare them with neurocysticercosis (NC) patients with mild CSF abnormalities by conducting a nine-year retrospective review at a neurological referral center. Two groups of patients were compared: group A, those with severe CSF pleocytosis > 1,000 cells/mm(3) (n = 12), and group B, those with CSF pleocytosis

Medical treatment for neurocysticercosis: drugs, indications and perspectives.

Neurocysticercosis is one of the most frequent parasitic diseases affecting the central nervous system. The introduction of anticysticidal therapy in the early 80's and the concomitant improvement of the radiological techniques have lead to apparently significant progress in patient prognosis. However, due to the specificity of the disease, a great debate has been generated on the real usefulness of cysticidal drugs. This article revises and discusses the pharmacological aspects of cysticidal treatment and summarizes current indications for the different types of the disease.

[Comparative analysis of the influence of food and cimetidine in plasma levels of praziquantel]. / Análisis comparativo de la influencia de los alimentos y la cimetidina en los niveles plasmáticos de prazicuantel.

Praziquantel (PZQ) is an effective drug for treatment of neurocysticercosis. The drug shows an extensive first-pass effect and therefore plasma levels are low. In order to increase plasma and CSF levels of PZQ other alternatives have been investigated such as the use of PZQ jointly with cimetidine or food. With the pharmacokinetic parameters obtained in these studies, in the present work computer simulations were made in order to predict plasma concentrations of PZQ-administration with cimetidine or with meals under the two treatments currently used: ultrashort scheme (three dose of 25 mg/kg given at 2-hours intervals) and the traditional scheme (50 mg/kg/day divided in three dose given at 8-hours intervals for 15 days). The results of our simulations showed that the combination of PZQ with a high carbohydrate diet could be an adequate alternative for clinical therapy. Furthermore a clinical study was performed in 18 patients with neurocysticercosis, which received the ultrashort scheme in fasting state, with cimetidine or with a high carbohydrate diet. The efficacy of the treatment was evaluated by the percentage of disappearance of the lesions and plasma levels obtained in each group. The results showed that a high carbohydrate diet increases plasma levels of PZQ. The results of the clinical study, together with our simulations indicate that the treatment of PZQ with a high carbohydrate diet was an adequate clinical alternative and showed improvement of the effectiveness of PZQ therapy.

Interaction between grapefruit juice and praziquantel in humans.

After a single oral dose of praziquantel with 250 ml of grapefruit juice, the area under the concentration-time curve and the maximum concentration in plasma of praziquantel (Cmax) were significantly increased (Cmax for water treatment, 637.71 +/- 128.5 ng/ml; and Cmax for grapefruit juice treatment, 1,037.65 +/- 305.7 ng/ml, P < 0.05). No statistically significant differences were found in the time to maximum concentration of drug in plasma or elimination half-life.