Islamic Bioethics: the Art of Decision Making

In Islam, bioethical decision-making is carried out within a framework of values derived from the revelation andtradition. Islamic bioethics or Islamic medical ethics are referring to Islamic guidance on ethics and moral issuesrelated to medical and scientific fields, especially those dealing with human, based from the Quran and Hadith.In Islam, human is one of the most sacred creatures of God. Therefore, he/she must be appreciated, respected andwell protected. Apparently, Muslim doctors have always been facing dilemmas on bioethical decision makingduring their practices. There are so many conflicting issues coming from multiple points of views such asdiscipline, legal, ethical, sharia, social, cultural and financial aspects. Muslim doctors should answer thedilemmas on each diagnosis and treatment intervention by having a good decision making as their first step. Byimplementing Islamic framework on bioethical decision making, guided by sharia which includes Quran,Hadith, Ijma, and Qiyas, it is expected that this framework will be able to assist Moslem doctors to solve theirdilemmas in this world and in the hereafter. A triangulation framework known as islamic bioethics consisting oftriangle I and triangle II will ease Moslem doctors to have the final decision for their daily medical practices.These triangle framework will be powerfull in use if combined with Prima Facie approach and a five-digitapproach

Hubungan Antara Indeks Produksi Retikulosit (IPR) Dengan Red Blood Cell Distribution Width (RDW) Pada Klasifikasi Anemia Berdasarkan Defek Fungsional

Reticulocyte Production Index (RPI) is a shift correction for the presence of reticulocyte that can assesses the real erythropoietic response of the bone marrow. RPI can be used to classify anemia as result from functional defect, i.e. RPI<2 for hypoproliferative and maturation defect anemia, and RPI>3 for hemolytic anemia. Measurement of Red Blood Cell Distribution Width (RDW) is the mathematical representation of variance within the size distribution of the red cell population. The objective of this study was to identify the variation of the red cell size within the population measured (anisocytosis) enable to determine the cell population as homogeneous (normal RDW) or heterogenous (increased or high RDW). The role of RDW to differentiate functional defect anemia with RPI<2 has not been studied. This study was done at Hematology Department Dr. Sardjito Hospital. In such a cross sectional study, the subjects were considered as anemic patients based on automated laboratory analyzer, peripheral blood smear, and reticulocyte count result. The result showed that seventy patients met the inclusion criteria. Sixty seven patients (95,71%) had RPI<2 classified as hypoproliferative and maturation defect anemia, 2 patients (2,85%) had RPI = 2-3 classified as borderline group and 1 patient (1,42%) had RPI>3 classified as hemolytic anemia. Means for reticulocyte count, corrected reticulocyte count, RPI, and RDW for hypoproliferative and maturation defect anemia were 2,8% and 2,3%; 1,1% and 1,1%; 0,4 and 0,5; 21,8% and 17,8% respectively, with p value by the Wilcoxon Signed Ranks Test are = 0,322; 0,52; 0,273; and 0,27 (CI = 95%). The proportion of anisocytosis and normocytosis for hypoproliferative anemia were 76,08% and 23,9% and for maturation defect anemia were 76,19% and 23,8% with Chi-Square test 0,000 and p = 0,993. No correlation between was observed RDW and RPI<2 with Spearman correlation (r = 0,0297 and p = 0,993). It is concluded that the use of RDW and RPI is not always useful to differentiate hypoproliferative and maturation defect anemia on the group of anemia categorized as RPI<2 without support from another laboratory test especially in combined anemia

Review-aggregated aspect-based sentiment analysis with ontology features

With all the information that is available on the World Wide Web, there is great demand for data mining techniques and sentiment analysis is a particularly popular domain, both in business and research. Sentiment analysis aims to determine the sentiment value, often on a positive–negative scale, for a given product or service based on a set of textual reviews. As fine-grained information is more useful than just a single overall score, modern aspect-based sentiment analysis techniques break down the sentiment and assign sentiment scores to various aspects of the product or service mentioned in the review. In this work, we focus on aspect-based sentim

An enhanced regimen as post-exposure chemoprophylaxis for leprosy:PEP+

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted)

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir