Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the rat

The pharmacokinetics of oxcarbazepine (30 mg kg-1, po), administered for 1 week, was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg-1, po). Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from dosing, using a sensitive HPLC method. No significant changes were observed in the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0-infinity) between the control and the pre-treated groups. The findings of this study suggest that OXC metabolism in the rat is apparently not affected by valproic acid, and the lack of effect may be attributed to the different pathways of biotransformation of the two drugs.     

Psychological distress,health and treatment-related factors among individuals initiating ART in Oromia,Ethiopia

HIV diagnosis may be a source of psychological distress. Late initiation of antiretroviral therapy (ART) and treatment-related beliefs may intensify psychological distress among those recently diagnosed. This analysis describes the prevalence of psychological distress among people living with HIV (PLWH) and examines the association of recent HIV diagnosis, late ART initiation and treatment-related beliefs with psychological distress. The sample includes 1175 PLWH aged 18 or older initiating ART at six HIV clinics in Ethiopia. Psychological distress was assessed with Kessler Psychological Distress Scale. Scores?≥?29 were categorized as severe psychological distress. Individuals who received their first HIV diagnosis in the past 90 days were categorized as recently diagnosed. Multivariable logistic regression modeled the association of recent diagnosis, late ART initiation and treatment-related beliefs on severe psychological distress, controlling for age, sex, education, area of residence, relationship status, and health facility. Among respondents, 29.5% reported severe psychological distress, 46.6% were recently diagnosed and 31.0% initiated ART late. In multivariable models, relative to those who did not initiate ART late and had longer time since diagnosis, odds of severe psychological distress was significantly greater among those with recent diagnosis and late ART initiation (adjusted OR [aOR]: 1.9 [95% CI 1.4, 2.8]). Treatment-related beliefs were not associated with severe psychological distress in multivariable models. Severe psychological distress was highly prevalent, particularly among those who were recently diagnosed and initiated ART late. Greater understanding of the relationship between psychological distress, recent diagnosis, and late ART initiation can inform interventions to reduce psychological distress among this population. Mental health screening and interventions should be incorporated into routine HIV clinical care from diagnosis through treatment.     

Frequency of small-colony variants and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in cystic fibrosis patients

Background

Small-colony variants (SCVs) are a distinct phenotype of Staphylococcus aureus, known for their role in chronic, difficult to treat infections, including cystic fibrosis (CF) lung disease. The goal of this study was to characterize SCV MRSA infection in an adult and pediatric CF population and to identify antibiotic susceptibility patterns unique to SCV MRSA.

High Risk of New Episode of Symptomatic Vasospasm in Unaffected Arteries in Subarachnoid Hemorrhage Patients Receiving Targeted Endovascular Treatment for Symptomatic Focal Vasospasm

Background

There is controversy whether asymptomatic vasospasm in other arteries should be concurrently treated (global treatment) in patients receiving targeted endovascular treatment [percutaneous-transluminal-angioplasty (PTA) and/or intra-arterial (IA) vasodilators] for focal symptomatic vasospasm.

Objective

To determine the rates of occurrence of new symptomatic vasospasm in previously asymptomatic arterial distributions among patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent targeted endovascular treatment for focal symptomatic vasospasm.

Methods

We identified all patients with SAH who had received targeted endovascular treatment during a 4-year period. We ascertained any new occurrence of symptomatic vasosopasm requiring endovascular treatment in previously unaffected (and untreated) arterial distributions within the same hospitalization. Blinded reviewers quantitatively graded angiographic vasospasm (<25, 26–49, ≥50 %) in all major arteries for each patient at the time of targeted treatment.

Results

Of the 41 patients who received targeted endovascular treatment (PTA in 41 % and vasodilators in 59 %), 11 (27 %) developed new symptomatic vasospasm in previously asymptomatic vascular distributions requiring endovascular treatment. Moderate severity of angiographic vasospasm in asymptomatic arteries at the time of targeted treatment tended to predict the occurrence of new symptomatic vasospasm. The rate of death and disability at discharge [modified Rankin scale (mRS) of 3–6] was 82 % (9/11) among those who developed a new episode of symptomatic vasospasm compared with 70 % (21/30) in those who did not (P = 0.58).

Conclusions

High risk of new occurrence of ischemic symptoms in previously asymptomatic (and untreated) arterial distributions among patients receiving targeted treatment should be recognized. Further studies should evaluate the benefit of performing global endovascular treatment during the initial targeted endovascular treatment session.     

SARS-CoV-2 infection and vaccination trigger long-lived B and CD4+ T lymphocytes with implications for booster strategies

BACKGROUNDImmunization against SARS-CoV-2, the causative agent of COVID-19, occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last.METHODSWe performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to 1 year after infection and following mRNA vaccination in naive individuals and individuals recovered from COVID-19 infection.RESULTSWe found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly, especially in naive individuals. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naive individuals, whereas it was ineffective in previously SARS-CoV-2–infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to 1 year following natural infection in a cohort of unvaccinated individuals.CONCLUSIONShort-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4⁺ T cells may protect from severe disease development. In naive individuals, a booster dose restored optimal anti-spike immunity, whereas the needs for vaccinated individuals who have recovered from COVID-19 have yet to be defined.FUNDINGThis study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018–2022), the University of Florence (project RICTD2122), the Italian Ministry of Health (COVID-2020-12371849), and the region of Tuscany (TagSARS CoV 2).     

Rapid micromethod for simultaneous measurement of oxcarbazepine and its active metabolite in plasma by high–performance liquid chromatography

A rapid method for the simultaneous determination of oxcarbazepine (OXC) and its active metabolite (10–hydroxycarbazepine) in human and rat plasma by reversed phase high–performance liquid chromatography is described. The method involves a simple one–step extraction of the drugs from plasma with dichloromethane. The extract was evaporated and the residue was reconstituted with mobile phase and injected onto a Novapak C₁₈ column. The eluting solvent was 20% aceto–nitrile in water at a flow rate of 1 5 ml/min and the detector was monitored at 215 nm. The detection limit of OXC and 10–hydroxycarbazepine was 50 and 20 ng/ml, respectively. The within–day and between–day coefficients of variation for OXC and its active metabolite were 2 57-6 95% and 4 21-8 3%, respectively. The relative and absolute recoveries varied between 71 4% and 104 0%. The applicability of the analytical procedure to pharmacokinetic studies was illustrated.     

Axillary sentinel node and tumour-related factors associated with non-sentinel node involvement in breast cancer

BACKGROUND: After completion of axillary dissection, many breast cancer patients with axillary sentinel nodal involvement are found to have regional disease limited to the sentinel nodes. These patients are exposed to the morbidity of axillary clearance without any expected therapeutic benefit. METHODS: Sentinel node biopsy was performed either with Patent blue dye or with a combined dye, radiocolloid and gamma-probe-guided method involving peritumoral tracer administration. For a series of 150 consecutive patients with involved axillary sentinel nodes and axillary dissection, factors associated with non-sentinel nodal involvement were analysed in a multivariate analysis based on logistic regression with the use of fractional polynomials. RESULTS: The following variables were found to be potentially associated with non-sentinel node metastases: tumour size, sentinel node metastasis size, number of examined sentinel nodes, percentage of involved sentinel nodes (the latter two were found to be significant only when in combination), and extracapsular perinodal spread. CONCLUSIONS: Isolated tumour cells and micrometastases in axillary sentinel nodes carry a low risk of non-sentinel node metastasis. The risk of metastasis to further echelon nodes is higher with macrometastases, especially if there is extracapsular growth and the proportion of involved sentinel nodes is high.     

Perception of dental fluorosis among adolescents living in urban areas of Ethiopia

The objective of the study was to assess the perception of dental fluorosis among adolescents residing in two urban areas in Ethiopia: Addis Ababa (low-fluoride drinking water) and Nazreth (high-fluoride drinking water). Students aged 12-15 years, enrolled in two junior secondary schools in Addis Ababa (n = 161) and two similar schools in Nazreth (n = 177) responded to evaluative statements concerning the appearance of anterior maxillary teeth. Color photographs depicting dental fluorosis (TF score 2, 3, 5 and 7) in maxillary front teeth were used as reference during structured interviews. A majority of the students from Addis Ababa and Nazreth were dissatisfied with the appearance of teeth having TF scores 2 and above. More than 66% of the students from both areas confirmed a need for dental consultation concerning fluorotic teeth with TF > or = [corrected] 2. As compared to their counterparts in Nazreth, children in Addis Ababa felt more embarrassed with TF score 2 and 3 (p < 0.01). TF scores 5 and 7 were found unacceptable both in Addis Ababa and in Nazreth. Students in Addis Ababa, more frequently than their counterparts in Nazreth, believed (erroneously) that dental fluorosis were related to neglect on the part of the child. The present findings confirm that fluorotic teeth constitute a social problem among junior secondary school children residing in low-fluoride as well as in high-fluoride urban areas in Ethiopia and, thereby, corroborate the public concern for safe drinking water.