scholarly journals Evaluating artesunate-amodiaquine deployment, efficacy and safety: an in silico pharmacological model

2019 ◽  
Author(s):  
Ki Bae Hong ◽  
Ian Hastings ◽  
Katherine Kay ◽  
Eva Maria Hodel
Keyword(s):  
Patient Adherence ◽  
Real Life ◽  
World Health ◽  
Fixed Dose ◽  
Multiple Treatment ◽  
Increased Risk ◽  
Dosing Regimens ◽  
Dose Combination ◽  
Health Organization ◽  
Pharmacological Model

AbstractBackgroundThe World Health Organization currently recommends artesunate-amodiaquine (AS-AQ) as a first-line treatment for uncomplicated falciparum malaria. The clinical efficacy of AS-AQ is very high but its effectiveness in the field varies considerably. This study aimed at comparing the efficacy, effectiveness and safety of AS-AQ fixed dose combination (FDC) and non-fixed formulation (non-FDC) in controlled and real-life settings using a pharmacological model of antimalarial treatment.MethodsThe effectiveness and safety of different drug formulations in different treatment scenarios were investigated using a pharmacological model of AS-AQ treatment. The model simulated multiple treatment scenarios to assess the effects of age-or weight-based dosing bands in three geographically distinct patient populations, and poor patient adherence.ResultsThe model output was consistent with clinical trials in terms of cure rates, recrudescence rates and the pattern of AQ overdosing with age- and weight-based dosing regimens. AS-AQ treatment has good efficacy and effectiveness in fully adherent patients but monotherapy of AS or AQ lead to treatment failure. The weight-based dosing regimen with FDC was the best option for patients in terms of drug safety and had similar efficacies to the other regimens. Asians were more likely to be overdosed with AQ when using age-based dosing regimens.ConclusionsWeight-based dosing is optimal but not always feasible, so age-based dosing regimens are often used as an alternative. The model outputs highlight the importance of optimising these age-based dosing regimens for specific regions, and identify an increased risk of overdosing in young children.

scholarly journals Fixed-dose Combination Therapy in Hypertension: Focus on Fixed-dose combination of Amlodipine and Valsartan (Exforge®)

2009 ◽  
Vol 1 ◽  
pp. CMT.S1982
Author(s):  
Shakil Aslam
Keyword(s):  
Combination Therapy ◽  
World Wide ◽  
Randomized Trials ◽  
Patient Adherence ◽  
Adult Population ◽  
Antihypertensive Agents ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Increased Risk ◽  
Dose Combination

Hypertension is the leading cause of disability and cardiovascular mortality world-wide. Approximately one-third of the US adult population and over a billion people world-wide have hypertension. Despite increased awareness of hypertension and availability of many effective antihypertensive agents, only one third of patients achieve their target blood pressure (BP). All expert panels now recommend use of combination therapy for stage 2 and higher hypertension and for individuals who are at increased risk of cardiovascular disease (CVD). Amlodipine, a dihydropyridine calcium channel blocker and Valsartan, an angiotensin II receptor (AT1-R) antagonist are widely used antihypertensive agents. Their efficacy in lowering systolic and diastolic BP and reducing CVD events has been demonstrated in several randomized trials. Fixed-dose combination of amlodipine and valsartan (A/V) has been shown to be more effective in lowering BP than monotherapy with either of these agents alone in randomized trials with comparable side effect profile. Approximately 80%-90% of patients with stage 1-2 hypertension receiving A/V fixed-dose combination achieve significant response, defined as a mean sitting diastolic BP < 90 mmHg or > 10 mmHg reduction from the baseline. Subgroup analyses show that A/V fixed-dose combination is equally effective in older individuals (>65), Blacks, in patients with isolated systolic hypertension, and in those who fail monotherapy. Furthermore, A/V fixed-dose combination is well tolerated and simplifies antihypertensive regimen enhancing patient adherence and a better BP control compared to monotherapy.

Simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol in fixed-dose combination antituberculosis pharmaceutical formulations: a review

2018 ◽  
Vol 10 (10) ◽  
pp. 1103-1116 ◽  
Author(s):  
M. A. L. Oliveira ◽  
P. R. Chellini ◽  
T. L. Amorim
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Pharmaceutical Formulations ◽  
World Health ◽  
Fixed Dose ◽  
First Line ◽  
The World ◽  
Dose Combination ◽  
Health Organization

According to the World Health Organization, rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride are the first-line drugs used to treat tuberculosis – an infectious disease caused by Mycobacterium tuberculosis.

scholarly journals KADAR SERUM GLUTAMIC OXALOACETAT TRANSAMINASE DAN SERUM GLUTAMIC PYRUVIC TRANSAMINASE PADA PASIEN TUBERKULOSIS PARU SELAMA DUA BULAN BERJALANNYA PEMBERIAN OBAT ANTI TUBERKULOSIS KOMBINASI DOSIS TETAP

e-CliniC ◽  
2014 ◽  
Vol 2 (3) ◽  
Author(s):  
Ayu R. Pribadini Nelwan ◽  
Stella Palar ◽  
Julia C. M. Lombo
Keyword(s):  
Pulmonary Tuberculosis ◽  
Serum Levels ◽  
Fixed Dose Combination ◽  
World Health ◽  
Fixed Dose ◽  
Glutamic Pyruvic Transaminase ◽  
Cross Sectional ◽  
The World ◽  
Dose Combination ◽  
Health Organization

Abstract: Tuberculosis (TB) is still a health problem around the world. According to statistics of the World Health Organization (WHO) showed that Indonesia’s ranking were down from third to fifth in the world. However there are also challenges in the treatment of tuberculosis worldwide and in Indonesia, like treatment failure, dropping out of treatment, and inappropriate treatment. This study aimed to compare the serum levels of SGOT (AST) and SGPT (ALT) in patients with pulmonary TB during two months administration of OAT KDT. This study was a cross sectional analytic study using secondary data and blood sample from patients with pulmonary TB. The samples in this study was patients with pulmonary tuberculosis, pulmonary tuberculosis first category, pulmonary tuberculosis BTA smear (+), pulmonary tuberculosis with controlled hypertension, pulmonary tuberculosis suspected MDR, pulmonary tuberculosis with secondary infections, pulmonary tuberculosis on treatment, and pulmonary tuberculosis which dropping put of treatment. The analysis of data changes on SGOT levels before and after administration of Anti-Tuberculosis Drugs (OAT) shows that the value of zcount: 2,223 >ztable: 1,645 with a significance value of p= 0,026 < 0,05. This indicates that there is an effect of the Anti Tuberculosis Drugs (OAT) fixed-dose combination toward SGOT levels. The analysis of data changes on SGPT levels before and after administration of Anti-Tuberculosis Drugs (OAT) shows that the value of zcount: 2,045 >ztable: 1,645 with a significance value of p= 0,041 < 0,05. This indicates that there is an effect of the Anti Tuberculosis Drugs (OAT) fixed-dose combination toward SGPT levels. There are a significant correlation between serum levels of glutamic oxaloacetat transaminase and glutamic pyruvic transaminase in patients with pulmonary tuberculosis during two months administration of anti-tuberculosis medication with a fixed-dose combination and an increasing levels of SGOT and SGPT in pulmonary tuberculosis patients.     Abstrak: Penyakit Tuberkulosis (TB) masih merupakan masalah kesehatan di dunia. Menurut data statistik World Health Organization (WHO) menunjukkan Indonesia turun dari peringkat tiga menjadi peringkat kelima dunia. Namun masih terdapat pula tantangan dalam pengobatan TB di dunia dan Indonesia, antara lain kegagalan pengobatan, putus pengobatan, dan pengobatan yang tidak tepat. Penelitian ini ditujukan untuk mengetahui perbandingan kadar serum SGOT dan SGPT pada pasien TB Paru selama dua bulan pemberian OAT KDT. Penelitian ini merupakan penelitian analitik cross sectional dengan menggunakan data sekunder dan pengambilan sampel darah pada pasien TB Paru. Pada penelitian ini sampel yang digunakan adalah penderita TB Paru, TB Paru kategori 1, TB paru BTA (+), TB Paru dengan Hipertensi terkontrol, TB paru suspek MDR, TB Paru dengan infeksi sekunder, TB paru on treatment, dan TB paru putus obat. Hasil analisis data perubahan kadar SGOT sebelum dan setelah diberikan Obat Anti Tuberkulosis menunjukkan bahwa nilai zhitung: 2,223 >ztabel : 1,645 dengan nilai signifikansi p= 0,026 < 0,05. Hal ini menunjukkan bahwa terdapat pengaruh pemberian Obat Anti Tuberkulosis (OAT) kombinasi dosis tetap terhadap kadar SGOT. Hasil analisis data perubahan kadar SGPT sebelum dan setelah diberikan Obat Anti Tuberkulosis menunjukkan bahwa nilai zhitung: 2,045 >ztabel : 1,645 dengan nilai signifikansi p= 0,041 < 0,05. Hal ini menunjukkan bahwa terdapat pengaruh pemberian Obat Anti Tuberkulosis (OAT) kombinasi dosis tetap terhadap kadar SGPT. Terdapat hubungan yang signifikan antara kadar serum glutamic oxaloacetic transaminase dan serum glutamic pyruvic transaminase pada pasien tuberkulosis paru selama dua bulan berjalannya pemberian obat anti tuberkulosis kombinasi dosis tetap dan terdapat peningkatan kadar SGOT dan SGPT pada pasien tuberkulosis paru.

scholarly journals Directly-Observed Intermittent Therapy versus Unsupervised Daily Regimen during the Intensive Phase of Antituberculosis Therapy in HIV Infected Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Gerardo Alvarez-Uria ◽  
Manoranjan Midde ◽  
Raghavakalyan Pakam ◽  
Praveen Kumar Naik
Keyword(s):  
Smoothing Splines ◽  
World Health ◽  
Fixed Dose ◽  
Intermittent Therapy ◽  
Continuous Variables ◽  
Intensive Phase ◽  
Antituberculosis Therapy ◽  
Increased Risk ◽  
The World ◽  
Health Organization

The World Health Organization strongly recommends using daily antituberculosis therapy (ATT) during the intensive phase for HIV infected patients. India has the highest burden of tuberculosis in the world, but HIV infected patients are still receiving intermittent ATT. In this study we compared the mortality in patients who received directly-observed intermittent ATT versus self-administered daily ATT with fixed dose combinations during the intensive phase in a context of freely available antiretroviral therapy. The study included 1460 patients, 343 in the intermittent ATT group and 1117 in the daily ATT group. Baseline covariates of the two groups were balanced using inverse probability of treatment weighting based on propensity score methods. In a sensitivity analysis, continuous variables (albumin, CD4 count, and age) were modelled using restricted cubic smoothing splines. Compared with patients who received daily ATT, patients who received intermittent ATT had a 40% higher risk of mortality (1.4 hazard ratio; 95% confidence interval, 1.14–1.7). We estimated that the use of daily ATT could achieve a 10% absolute reduction in mortality at 12 months. Self-administered daily ATT was not associated with an increased risk of default from treatment. These results support the immediate implementation of daily ATT for HIV infected patients during the intensive phase in India.

Antidiabetics: Structural Diversity of Molecules with a Common Aim

2018 ◽  
Vol 25 (18) ◽  
pp. 2140-2165 ◽  
Author(s):  
Jelena B. Popovic-Djordjevic ◽  
Ivana I. Jevtic ◽  
Tatjana P. Stanojkovic
Keyword(s):  
Structural Diversity ◽  
World Health ◽  
Common Disease ◽  
Peroxisome Proliferator ◽  
Epidemic Disease ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Health Organization

Background: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability. Methods: A systematic search of peer-reviewed scientific literature and public databases has been conducted. We included the most recent relevant research papers and data in respect to the focus of the present review. The quality of retrieved papers was assessed using standard tools. Results: The review highlights the chemical structural diversity of the molecules that have the common target-DMT2. So-called traditional antidiabetics as well as the newest and the least explored drugs include polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1, dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives, benzylthiazolidine- 2,4-diones (peroxisome proliferator activated receptor-γ agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules (α-glucosidase and sodium/ glucose co-transporter 2 inhibitors). Conclusion: As diabetes becomes a more common disease, interest in new pharmacological targets is on the rise.

scholarly journals Newborns at risk of Covid-19 ― lessons from the last year

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Malika D. Shah ◽  
Ola Didrik Saugstad
Keyword(s):  
Horizontal Transmission ◽  
Mode Of Delivery ◽  
Newborn Infants ◽  
World Health ◽  
Premature Delivery ◽  
Mortality And Morbidity ◽  
Skin Contact ◽  
Cord Clamping ◽  
Increased Risk ◽  
Health Organization

Abstract After more than 1 year of the SARS-CoV-2 pandemic, a great deal of knowledge on how this virus affects pregnant women, the fetus and the newborn has accumulated. The gap between different guidelines how to handle newborn infants during this pandemic has been minimized, and the American Academy of Pediatrics (AAP)’s recommendations are now more in accordance with those of the World Health Organization (WHO). In this article we summarize present knowledge regarding transmission from mother to the fetus/newborn. Although both vertical and horizontal transmission are rare, SARS-CoV-2 positivity is associated with an increased risk of premature delivery and higher neonatal mortality and morbidity. Mode of delivery and cord clamping routines should not be affected by the mother’s SARS-CoV-2 status. Skin to skin contact, rooming in and breastfeeding are recommended with necessary hygiene precautions. Antibodies of infected or vaccinated women seem to cross both the placenta and into breast milk and likely provide protection for the newborn.

scholarly journals Proposal of initial and maintenance dosing regimens with linezolid for renal impairment patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hitoshi Kawasuji ◽  
Yasuhiro Tsuji ◽  
Chika Ogami ◽  
Kou Kimoto ◽  
Akitoshi Ueno ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Standard Dose ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Clinical Failure ◽  
Therapeutic Concentration ◽  
Reduced Dose ◽  
Increased Risk ◽  
Dosing Regimens ◽  
Multivariable Analyses

Abstract Background Linezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment. Methods We retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration (Cmin) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of Cmin-based TDM (TDM group) or not (non-TDM group) during linezolid treatment. Results In the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10–9.12) and higher Cmin. Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed Cmin ≥ 2.0 mg/L. Additional analysis of 53 episodes in which Cmin was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group. Conclusions Empirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and Cmin-based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.

scholarly journals Covid-19 and Acute Kidney Injury: Recent Updates

2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Salman Tahir Shafi
Keyword(s):  
Acute Kidney Injury ◽  
Severe Acute Respiratory Syndrome ◽  
World Health Organization ◽  
Recent Literature ◽  
Kidney Injury ◽  
World Health ◽  
Related Disease ◽  
Increased Risk ◽  
The World ◽  
Health Organization

In January 2020, the pathogen was identified and named by the World Health Organization as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2). The consequent SARS-CoV-2-related disease was defined as coronavirus disease 2019 (COVID-19). As data emerged about characteristics of the disease, it was found to be associated with increased risk of acute kidney injury (AKI). We explore the recent literature and reports emerging from the epicenters of the pandemic to help our viewers understand the nature of AKI among these patients. 

scholarly journals High global consumption of potentially inappropriate fixed dose combination antibiotics: Analysis of data from 75 countries

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0241899
Author(s):  
Barbara Bortone ◽  
Charlotte Jackson ◽  
Yingfen Hsia ◽  
Julia Bielicki ◽  
Nicola Magrini ◽  
...  
Keyword(s):  
The United States ◽  
Antibiotic Consumption ◽  
Essential Medicines ◽  
World Health ◽  
Fixed Dose ◽  
Middle Income ◽  
Us Fda ◽  
Analysis System ◽  
Health Organization ◽  
Data Analysis System

Antibiotic fixed dose combinations (FDCs) can have clinical advantages such as improving effectiveness and adherence to therapy. However, high use of potentially inappropriate FDCs has been reported, with implications for antimicrobial resistance (AMR) and toxicity. We used a pharmaceutical database, IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS®), to estimate sales of antibiotic FDCs from 75 countries in 2015. Antibiotic consumption was estimated using standard units (SU), defined by IQVIA as a single tablet, capsule, ampoule, vial or 5ml oral suspension. For each FDC antibiotic, the approval status was assessed by either registration with the United States Food and Drug Administration (US FDA) or inclusion on the World Health Organization (WHO) Essential Medicines List (EML). A total of 119 antibiotic FDCs were identified, contributing 16.7 x 109 SU, equalling 22% of total antibiotic consumption in 2015. The most sold antibiotic FDCs were amoxicillin-clavulanic acid followed by trimethoprim/sulfamethoxazole and ampicillin/cloxacillin. The category with the highest consumption volume was aminopenicillin/β-lactamase inhibitor +/- other agents. The majority of antibiotic FDCs (92%; 110/119) were not approved by the US FDA. Of these, the most sold were ampicillin/cloxacillin, cefixime/ofloxacin and metronidazole/spiramycin. More than 80% (98/119) of FDC antibiotics were not compatible with the 2017 WHO EML. The countries with the highest numbers of FDC antibiotics were India (80/119), China (25/119) and Vietnam (19/119). There is high consumption of FDC antibiotics globally, particularly in middle-income countries. The majority of FDC antibiotic were not approved by either US FDA or WHO EML. International initiatives such as clear guidance from the WHO EML on which FDCs are not appropriate may help to regulate the manufacturing and sales of these antibiotics.

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