Neuroethics and cultural context: The case of electroconvulsive therapy in Argentina.

As neuroethics continues to grow as an established discipline, it has been charged with not being sufficiently sensitive to the way in which the identification, conceptualization, and management of the ethical issues raised by neuroscience and its applications are shaped by local systems of knowledge and structures. Recently there have been calls for explicit recognition of the role played by local cultural contexts and for the development of cross-cultural methodologies that can facilitate meaningful cultural engagement. In this article, we attempt to fill this perceived gap by providing a culturally situated analysis of the practice of electroconvulsive therapy (ECT) in Argentina. ECT was introduced as a psychiatric treatment in Argentina in the 1930s but it is largely underutilized. While the use of ECT remains low in several countries, what makes the Argentinian case interesting is that the executive branch of government has taken a stance regarding both the scientific and moral appropriateness of ECT, recommending its prohibition. Here, we begin with a recent controversy over the use of ECT in Argentina and explain the legal recommendation to ban its application. Next, we offer an overview of some of the salient aspect of the international and local discussions on ECT. We argue that the governmental recommendation to ban the procedure should be rethought. While acknowledging the role that contexts and local conditions play in shaping the identification and assessment of the relevant ethical issues, we caution against using contextual and cultural considerations to avoid a necessary ethical debate on controversial issues.

Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1-infected naive patients with high CD4 counts.

OBJECTIVES: To investigate the value of tropism (determined by genotypic testing) to predict CD4 depletion in HIV-infected antiretroviral-naive patients with high CD4 counts. METHODS: Viral tropism was determined by geno2pheno (false positive rate = 10%) in 223 HIV-infected subjects naive to antiretrovirals with CD4 count ≥350 cells/µL and HIV-RNA >500 copies/mL enrolled in the ICONA Foundation Study for whom a stored plasma sample (baseline) was retrospectively tested. We monitored CD4 cell count and identified predictors of decline before antiretroviral therapy initiation, applying a mixed linear model with covariates (age, gender, tropism, HIV risk factor, calendar year of HIV infection, months from HIV diagnosis to baseline, hepatitis C virus status, CD4 and HIV-RNA at sample collection and duration of follow-up). RESULTS: Two hundred and twenty-three subjects met the eligibility criteria; 137 (61%) were male and the median age was 35 (31-40) years. Median follow-up was 16.4 (3.2-37.2) months. Median CD4 decrease during follow-up was -157 (-278 to -13) cells/µL. At baseline, 192 (86%) subjects were defined as harbouring R5 virus and 31 (14%) non-R5. Median CD4 count was 571 (458-729) cells/µL and median HIV-RNA was 4.08 (3.57-4.55) log(10) copies/mL. At multivariable analysis, a greater mean CD4 decrease was associated with non-R5 viral tropism (-159.9 ± 12.22, P = 0.0002) at baseline. Other significant covariates were female gender, older age, intravenous drug use, longer duration of follow-up, and higher CD4 cell count and higher HIV-RNA at sample collection. CONCLUSIONS: In patients with CD4 counts ≥350 cells/µL, non-R5 viral tropism by geno2pheno is predictive of CD4 decrease independent of their viral set point and CD4 counts.

Calidad de vida y sarcopenia en pacientes adultos con insuficiencia renal crónica / Quality of life and sarcopenia in adult patients with chronic renal failure

RESUMEN Introducción: la calidad de vida puede alterarse en los pacientes con insuficiencia renal crónica, sobre todo si sufren concomitantemente de sarcopenia. Objetivo: determinar la relación entre sarcopenia y calidad de vida en pacientes adultos con insuficiencia renal crónica del Hospital Nacional (Itauguá) y Hospital Militar (Asunción) entre abril y noviembre del 2021. Metodología: se utilizó un diseño observacional, descriptivo, transversal. Se incluyó a sujetos adultos de ambos sexos, portadores de insuficiencia renal crónica. Se midieron variables antropométricas, clínicas y laboratoriales. La calidad de vida se evaluó con el cuestionario EQ-5D y la sarcopenia con la fuerza de prensión palmar y el índice de masa muscular. Los datos se sometieron a estadística descriptiva y analítica con el programa Epi Info 7™. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este, Paraguay. Resultados: ingresaron al estudio 62 varones con edad media 56 ± 15 años y 57 mujeres con edad media 51 ± 16 años. La más frecuente de la insuficiencia renal fue la hipertensión arterial asociada a la diabetes mellitus (45,4 %). La sarcopenia se confirmó en 38,6 % de los pacientes. La calidad de vida fue buena en 30,25 %, regular en 39,5 % y mala en 30,25 %. Conclusión: en pacientes adultos con insuficiencia renal crónica, la sarcopenia predominó en los sujetos con regular y mala calidad de vida.

ABSTRACT Introduction: the quality of life can be altered in patients with chronic renal failure, especially if they suffer concomitantly from sarcopenia. Objective: to determine the relationship between sarcopenia and quality of life in adult patients with chronic renal failure at the Hospital Nacional (Itauguá) and the Hospital Militar (Asunción) between April and November 2021. Methodology: an observational, descriptive, cross-sectional design was used. Adult subjects of both sexes, carriers of chronic renal failure were included. Anthropometric, clinical and laboratory variables were measured. Quality of life was evaluated with the EQ-5D questionnaire and sarcopenia with palm grip strength and muscle mass index. The data was submitted to descriptive and analytical statistics with the Epi Info 7™ program. The study was approved by the Ethics Committee of the Universidad Privada del Este, Paraguay. Results: 62 men with a mean age of 56 ± 15 years and 57 women with a mean age of 51 ± 16 years entered the study. The most frequent renal failure was arterial hypertension associated with diabetes mellitus (45.4 %). Sarcopenia was confirmed in 38.6 % of the patients. The quality of life was good in 30.25 %, regular in 39.5 % and bad in 30.25 %. Conclusion: in adult patients with chronic renal failure, sarcopenia prevailed in subjects with fair and poor quality of life.

Comparison of a rule-based algorithm with a phenotype-based algorithm for the interpretation of HIV genotypes in guiding salvage regimens in HIV-infected patients by a randomized clinical trial: the mutations and salvage study.

BACKGROUND: There is still considerable uncertainty as to the best algorithm for interpreting human immunodeficiency virus (HIV) genotyping results. METHODS: A total of 318 subjects with HIV RNA levels of >1000 copies/mL were enrolled in 41 centers throughout Italy from 2001 through 2003, stratified on the basis of their drug history, randomized (1:1) to 2 arms to have their treatments modified on the basis of the results of HIV genotyping (as interpreted by virtual phenotype analysis or with use of a rule-based interpretation system), and followed up for 48 weeks. At least 1 nucleoside reverse-transcriptase inhibitor and 1 protease inhibitor had to be included in any new regimen; nonnucleoside reverse-transcriptase inhibitor-naive patients were also prescribed a nonnucleoside reverse-transcriptase inhibitor. Only drugs licensed in Italy were allowed. The primary end point was a decrease in HIV RNA level to <400 copies/mL by week 12 according to on-treatment analysis. RESULTS: The mean (+/- standard deviation) values at baseline were as follows: HIV RNA level, 4.1+/-0.74 log(10) copies/mL; CD4(+) T lymphocyte count, 410+/-262 cells/microL; reverse-transcriptase mutations, 4.8+/-2.9; and protease mutations, 2.8+/-2.5. There were 133 patients (41.8%) who were nonnucleoside reverse-transcriptase inhibitor naive and protease inhibitor experienced, 63 patients (19.8%) who were nonnucleoside reverse-transcriptase inhibitor experienced and protease inhibitor naive, and 122 patients (38.4%) who were 3-class experienced. A total of 192 patients completed 12 weeks of the treatment regimen assigned at baseline; at 12 weeks, 66.3% of patients in the virtual phenotype arm and 71.3% of patients in the rule-based interpretation arm had HIV RNA levels of <400 copies/mL (P = .46). No statistically significant difference between arms was observed by intention-to-treat analysis. CONCLUSION: Both the virtual phenotype and rule-based interpretation methods of HIV genotyping can guide the selection of effective antiretroviral drugs for a salvage regimen.

Brief Report: Consequences of Presentation With Advanced HIV Disease in Pregnancy: Data From a National Study in Italy.

Among 469 women with a diagnosis of HIV in pregnancy, 74 (15.8%) presented with less than 200 CD4 cells per cubic millimeter. The only variable significantly associated with this occurrence was African origin (odds ratio: 2.22, 95% confidence intervals: 1.32 to 3.75, P = 0.003). Four women with low CD4 (5.6%), compared with none with higher CD4 counts, had severe AIDS-defining conditions (P < 0.001) during pregnancy or soon after delivery, and one transmitted HIV to the newborn. Early preterm delivery (<32 weeks) was significantly more frequent with low CD4 (6.2% vs. 1.4%, P = 0.015). An earlier access to HIV testing, particularly among immigrants of African origin, can prevent severe HIV-related morbidity.

Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects.

In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV+) patients coinfected with HCV. A total of 119 HIV+ subjects were included in our study: 67 HIV+ patients, 32 HIV+ and HCV-positive (HCV+) patients without cirrhosis, and 20 HIV+ and HCV+ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV+ and HCV+ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV+ and HCV-negative individuals (28 and 58% lower, respectively; P < 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (P < 0.05) in HIV+ and HCV+ subjects with cirrhosis (0.06 +/- 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV+ and HCV-negative patients (0.16 +/- 0.13) and HIV+ and HCV+ patients without cirrhosis (0.24 +/- 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV+ and HCV+ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.

Limited sampling strategy for the estimation of systemic exposure to the protease inhibitor nelfinavir.

Therapeutic drug monitoring (TDM) of antiretroviral drugs has been proposed as a means of optimizing response to highly active antiretroviral therapy (HAART) in HIV infection because suboptimal exposure to these agents may lead to the development of resistant viral strains and subsequent therapeutic failure. The area under the curve (AUC), though considered to make the best estimate of total drug exposure, requires repeated blood sampling. The authors investigated the predictability of individual nelfinavir (NFV) concentrations at different time points for the AUC and tried to find the best sampling time for the abbreviated AUC to predict NFV total body exposure. A total of 99 NFV AUC0-12h values were measured in 99 patients receiving a 1250-mg oral dose twice a day. Venous blood samples were collected at baseline (predose, 0) and 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose. A stepwise forward-selection, multiple-regression technique was chosen to assess the relative importance of single and combination concentration time points to predict the AUC calculated from the entire pharmacokinetic profile. Data were split into a development set and a validation set. The development set contained 49 randomly selected HIV patients. Of these, 22 HIV patients were coinfected with HCV, 7 with and 15 without cirrhosis. One-point predictors provided the lowest prediction precision, but predictive performance improved after the first 2 hours postdose. Plasma concentrations at 0 and 4 hours after the oral dose were most predictive if 2 variables were used in the regression equation. The AUC could be estimated from data for these 2 samples by using the following equation: AUC0-12 = 3.0 + 2.7 (C0) + 6.4 (C4), r = 92. The predictive performance of 2-point predictors at 0 and 4 hours (C0 + C4) was validated by comparing their ability to predict the full AUC in a validation set representative of HIV/HCV patients (n = 28) and HIV/HCV patients, with (n = 8) and without (n = 14) cirrhosis. The results showed a mean bias ranging from +2.7% in HIV/HCV patients to -6.0% in HCV coinfection with cirrhosis. The authors conclude that this result is clinically significant. The limited sampling strategy (LSS) described could be used in clinical practice for the easy assessment of the total exposure to NFV in HIV/HCV patients, both with and without cirrhosis.