Elimination Phase Research Articles

A two-sample approach to retrograde extrapolation of blood THC concentrations – Is it feasible?

BackgroundRetrograde extrapolation of drug concentrations in blood can be relevant in cases of drug-impaired driving and is regularly used in forensic toxicology in Norway. Δ9-tetrahydrocannabinol (THC) has complex, multi-compartmental pharmacokinetics, which makes retrograde extrapolation of blood THC concentrations problematic. In the present study, we evaluated an approach to retrograde extrapolation in which momentary rates of decrease of THC were estimated from two consecutive blood samples in apprehended drivers. Material and methodsData were collected from apprehended drivers in Norway 2000–2020. We included 548 cases in which THC was detected in two consecutive blood samples collected ≥ 20 min apart. THC concentrations were measured by GC-MS and UHPLC-MS/MS. In each case, THC concentrations and the time between the two sampling points (Δt) were used to estimate the rate constant k. The relationship between THC concentration and k was modelled by linear regression. ResultsThe median Δt was 31 min (interquartile range, IQR = 9). The median blood THC concentration was 2.4 μg/L (IQR = 3.4) at the first sampling point and 2.3 μg/L (IQR =3.1) at the second. The concentration decreased in 62% and increased in 38% of all cases. However, considering measurement uncertainty, the changes were not statistically significant in 87% of cases. The mean of k was 0.12 h-1, corresponding to an apparent t1/2 of 6.0 h. The t1/2 predicted from linear regression of k against THC concentration ranged from 0.93 to 13 h for the highest and lowest concentrations observed (36 and 0.63 μg/L, respectively). The time from driving to blood collection had a median of 1.7 h (IQR = 1.5), and did not correlate with k. ConclusionsThe apparent t1/2 of THC calculated from the mean of k was 6.0 h, which is shorter than the terminal elimination t1/2 suggested in previous population studies. This indicates that blood samples were often taken during the late distribution phase of THC. Because Δt was short relative to the rates of decrease expected in the late distribution and elimination phases, the underlying true concentration changes related to in vivo pharmacokinetics were small and masked by the relatively larger “false” changes introduced by random analytical and pre-analytical error. Therefore, individual values of k calculated from only two blood samples taken a short time apart are unreliable, and a two-sample approach to retrograde extrapolation of THC cannot be recommended.

Absence of Asymptomatic Malaria Reservoirs in an Area with a Previous History of Local Malaria Transmission: A Successful Experience in Line with the Malaria Elimination Program in Iran.

Asymptomatic malaria is a major challenge to be addressed in the implementation of the malaria elimination program. The main goal of the malaria surveillance system in the elimination phase is to identify reliably all the positive cases of malaria reliably (symptomatic and asymptomatic) in the shortest possible time. This study focused on the monitoring of asymptomatic malaria reservoirs in areas where local transmission had been previously established. It was a case-study approach that was conducted in the Anarestan area. A total of 246 residents and immigrants living in the area at the age range of 4-60 years old were randomly selected to be tested for malaria by microscope, RDT, and nested-PCR techniques. The inclusion criterion for participants to be entered into the study was the absence of specific symptoms of malaria. Moreover, participants who have been taking antimalarials for the last month were excluded from the study. The results indicated no positive cases of asymptomatic malaria among the participants tested by all methods. The results of this study have shown that, without concerns for asymptomatic parasitic patients, a malaria elimination program has been successfully implemented within the studies area. In addition, the findings emphasized the existence of a strong malaria surveillance system in this area.

Characterization aspects of Cerium(III)ironmolybdophosphate and Cerium(III)aluminomolybdophosphate: A comparative study

In the current study, two ion exchangers named Cerium(III)ironmolybdophosphate and Cerium(III)aluminomolybdophosphate were synthesized and then elemental, morphological and spectral properties of the constructed materials were characterized by employing FTIR, SEM and TGA techniques. The obtained XRD results revealed the crystalline nature of the grown materials with lacunar keggin geometry. These two ionophores exhibited remarkable ion exchange capacities (IECs) of 5.76 ± 0.1 and 5.6 ± 0.2 meqgm−1 respectively. Subsequently, distribution coefficients (Kd) were determined, and finally, the grown ion exchangers demonstrated their selective nature towards Zr4+ ions at a high phase of elimination for all metallic ions. Thus, these synthesized materials exhibit appreciable ion interchangeable active sites that can be employed selectively for Zr4+ ions in solution at micro-level quantitative analysis.

Parameter identification of fuel cell using Repairable Grey Wolf Optimization algorithm

The performance of population-based meta-heuristic algorithms can be divided into two phases: exploitation and exploration. However, a major drawback of these methods is their inability to guarantee thorough searching of the entire search space. This is because the population (wolves) is randomly distributed and may not cover all areas in searching for the best solution. To address this issue, this paper introduces a simple technique called Repairable Grey Wolf Optimization (RGWO), which can be easily integrated into any population-based algorithm to enhance the exploration phase. The RGWO is implemented within the Grey Wolf Optimization (GWO) method and involves two main phases: elimination and search space management. In the elimination phase, underperforming wolves are gradually replaced with new ones, and new design parameters are introduced to improve the control of exploitation and exploration. In the search space management phase, instead of initially spreading the wolves across the entire search space, they are concentrated in a small portion and gradually expand from there. To evaluate the effectiveness of this approach, an extensive comparative study was conducted, comparing it with various classic and state-of-the-art meta-heuristic optimization algorithms. The results demonstrate several advantages over existing techniques, including fast convergence and high robustness.

Toxicokinetics of praseodymium and cerium administered as chloride salts in Sprague-Dawley rats: impacts of the dose and of co-exposure with additional rare earth elements.

We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl3 or CeCl3 at 0.3or1mg/kgbw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group). In blood, Pr and Ce half-lives for the initial phase (t1/2α) increased with increasing doses, while their half-lives for the terminal phase (t1/2β) were similar at both doses. In urine, a minor excretion route, no significant effect of the dose on the cumulative excretion was apparent. In feces, a major excretion route, the fraction of the Pr dose recovered was significantly lower at the 1mg/kg bw dose compared to the 0.3mg/kgbw dose, while no significant dose effect was apparent for Ce. In the liver and spleen, which are the main sites of REEs accumulation, there was a significant effect of the dose only for Ce retention in the spleen (i.e., increased retention of Ce in spleen at higher dose). Results were compared with those of a previous toxicokinetic study with a similar design but an exposure to a quaternary mixture of CeCl3, PrCl3, NdCl3 and YCl3, each administered at 0.3mg/kgbw or 1mg/kgbw. A mixture effect was apparent for the initial elimination phase (t1/2α) of Pr and Ce from blood and forthe fecal excretion of Ce at the 1mg/kg bw. In urine and liver, there was no evident overall mixture effect; in the spleen, there was a higher retention of Pr and Ce in rats exposed to the mixture at the 0.3mg/kgbw, but not at the 1mg/kgbw dose. Overall, this study showed that the dose and mixture exposure are two important factors to consider as determinants of the toxicokinetics of REEs.

Immune evasion by cancer stem cells ensures tumor initiation and failure of immunotherapy

Cancer stem cells (CSCs) are a small subpopulation of cells that drive the formation and progression of tumors. However, during tumor initiation, how CSCs communicate with neighbouring immune cells to overcome the powerful immune surveillance barrier in order to form, spread, and maintain the tumor, remains poorly understood. It is, therefore, absolutely necessary to understand how a small number of tumor-initiating cells (TICs) survive immune attack during (a) the “elimination phase” of “tumor immune-editing”, (b) the establishment of regional or distant tumor after metastasis, and (c) recurrence after therapy. Mounting evidence suggests that CSCs suppress the immune system through a variety of distinct mechanisms that ensure the survival of not only CSCs but also non-stem cancer cells (NSCCs), which eventually form the tumor mass. In this review article, the mechanisms via which CSCs change the immune landscape of the tissue of origin, which contains macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, and tumor-infiltrating lymphocytes, in favour of tumorigenesis were discussed. The failure of cancer immunotherapy might also be explained by such interaction between CSCs and immune cells. This review will shed light on the critical role of CSCs in tumor immune evasion and emphasize the importance of CSC-targeted immunotherapy as a cutting-edge technique for battling cancer by restricting communication between immune cells and CSCs.

Elimination of malaria from Sri Lanka and beyond; lessons for other countries in elimination phase

Elimination of malaria in 2012 was a major achievement in post-independent Sri Lanka. Sri Lanka missed a golden opportunity in 1963 when only 17 cases of malaria were reported in the country, but could not sustain the momentum resulting in a major resurgence in 1967/69. With the resurgence, the then malaria eradication programme was reverted back to a control programme that lasted for another 30 years. The WHO’s Roll Back Malaria Initiative launched in 1998 provided a renewed interest in malaria control and subsequent elimination. With targeted control activities, the burden of malaria started to decrease since year 2000. Although Sri Lanka had reached pre-elimination status as early as 2004, the ongoing separatist war at that time prevented a country-wide elimination drive being implemented. With cessation of hostilities in 2009 and Global Fund financing, both of which were crucial inputs, an elimination drive was launched in September 2009 which eventually eliminated indigenous malaria in November 2012 with malaria-free certification by WHO being obtained in September 2016. Since malaria elimination, the country forged on to the prevention of re-establishment phase primarily focusing on good public health practice that included intensified surveillance, both parasitological and entomological; quality assured diagnostic and treatment services; and advocacy at various levels including doctors. Despite these measures, an introduced case and a transfusion induced case of malaria have been reported. A new vector of urban malaria, Anopheles stephensi, was reported in December 2016. Prevention of re-establishment of malaria should be kept in the radar of public health until malaria is eradicated.

Elimination of malaria from Sri Lanka and beyond; lessons for other countries in elimination phase.

Elimination of malaria in 2012 was a major achievement in post-independent Sri Lanka. Sri Lanka missed a golden opportunity in 1963 when only 17 cases of malaria were reported in the country, but could not sustain the momentum resulting in a major resurgence in 1967/69. With the resurgence, the then malaria eradication programme was reverted back to a control programme that lasted for another 30 years. The WHO's Roll Back Malaria Initiative launched in 1998 provided a renewed interest in malaria control and subsequent elimination. With targeted control activities, the burden of malaria started to decrease since year 2000. Although Sri Lanka had reached pre-elimination status as early as 2004, the ongoing separatist war at that time prevented a country-wide elimination drive being implemented. With cessation of hostilities in 2009 and Global Fund financing, both of which were crucial inputs, an elimination drive was launched in September 2009 which eventually eliminated indigenous malaria in November 2012 with malaria-free certification by WHO being obtained in September 2016. Since malaria elimination, the country forged on to the prevention of re-establishment phase primarily focusing on good public practice that included intensified surveillance, both parasitological and entomological; quality assured diagnostic and treatment services; and advocacy at various level including doctors. Despite these measures, an introduced case and an induced case of malaria have been reported. A new vector of urban malaria, Anopheles stephensi, was reported in December 2016. Prevention of re-establishment of malaria should be kept in the radar of public health until malaria is eradicated.

Influence of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine in adult patients receiving CHOP therapy.

This study aims to clarify the impact of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine (VCR) in adult patients receiving CHOP therapy. Plasma samples were collected immediately after the end of VCR administration and at 1.5, 2.5, 3.5, 5.5, 9.5, 13.5, and 25.5h after the start of administration. Areas under the plasma concentration-time curves of VCR in the elimination phase (AUC1.5-25.5) were calculated using the linear trapezoidal rule. Half-lives of VCR during the early phase (1.5-5.5h) and terminal phase (5.5-25.5h; t1/2γ) were determined according to the log-linear regression of the concentration-time data for at least 3 sampling points. A total of 41 adult patients were enrolled in this study. The median t1/2γ and AUC1.5-25.5 were significantly longer and higher in CYP3A5 non-expressers (CYP3A5*3/*3) than in CYP3A5 expressers (CYP3A5*1/*1 or *1/*3) (21.3 vs 13.8h, P = 0.005 and 35.5 vs 30.0ng･h/mL, P = 0.006, respectively). Conversely, there were no significant differences in pharmacokinetic parameters among the ABCB1 c.1236C>T, c.2677G>A/T, c.3435C>T genotype groups. A stepwise selection multiple linear regression analysis showed that the dose of VCR administered and CYP3A5 non-expresser status were independent factors influencing the AUC1.5-25.5 (partial R2 = 0.212, P = 0.002 and partial R2 = 0.143, P = 0.010, respectively). The CYP3A5*3 polymorphism was found to be an indicator for predicting exposure to VCR in adult patients receiving CHOP therapy. This information may be useful for the individualization of VCR dosages.

Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses.

Cannabidiol (CBD) products gain increasing popularity amongst animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equine sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was to determine the pharmacokinetic properties of CBD following oral administration in the horse to assist doping control laboratories with interpreting CBD analytical results. Part 1: dose escalation study: Single oral administration of three escalating doses of CBD paste (0.2 mg/kg, n = 3 horses; 1 mg/kg, n = 3; 3 mg/kg, n = 5) with >7 days wash-out periods in between. Part 2: multiple dose study: oral administration of CBD paste (3 mg/kg, n = 6) twice daily for 15 days. Multiple blood and urine samples were collected daily throughout both studies. Following study part 2, blood and urine samples were collected for 2 weeks to observe the elimination phase. Concentrations of CBD, its metabolites and further cannabinoids were evaluated using gas-chromatography/tandem-mass-spectrometry. Pharmacokinetic parameters were assessed via two approaches: population pharmacokinetic analysis using a nonlinear mixed-effects model and non-compartmental analysis. AUC0-12 h and Cmax were tested for dose proportionality. During the elimination phase, the CBD steady-state urine to serum concentration ratio (Rss) was calculated. Oral CBD medication was well-tolerated in horses. Based on population pharmacokinetics, a three-compartment model with zero-order absorption most accurately described the pharmacokinetic properties of CBD. High volumes of distribution into peripheral compartments and high concentrations of 7-carboxy-CBD were observed in serum. Non-compartmental analysis identified a Cmax of 12.17 ± 2.08 ng/mL after single administration of CBD (dose: 3 mg/kg). AUC0-12 h showed dose proportionality, increase for Cmax leveled off at higher doses. Following multiple doses, the CBD terminal half-life was 161.29 ± 43.65 h in serum. Rss was 4.45 ± 1.04. CBD is extensively metabolized and shows high volumes of tissue distribution with a resulting extended elimination phase. Further investigation of the potential calming and anti-inflammatory effects of CBD are required to determine cut-off values for medication control using the calculated Rss.

STOCHASTIC DYNAMICS BETWEEN THE IMMUNE SYSTEM AND CANCER CELLS WITH ALLEE EFFECT AND IMMUNOTHERAPY

In this work, we use continuous-time Markov jump processes and the corresponding zero fluctuation ordinary differential equations to analyze the relation between immune response and cancerous cells. We incorporate the Allee effect into our model to show that intrinsic stochasticity and nonlinearity may interact in elimination, equilibrium, and escape mechanisms in the low-count regime. Later, we consider the effect of immunotherapy through a pulse injection term and the Tau-Leaping algorithm. We show using the model state variables and parameters that the cancer cell population at its threshold level gets into the elimination phase for high antigenicity values.

Pharmacokinetics, biodistribution and toxicology of novel cell-penetrating peptides

Cell-penetrating peptides (CPPs) have been used in basic and preclinical research in the past 30 years to facilitate drug delivery into target cells. However, translation toward the clinic has not been successful so far. Here, we studied the pharmacokinetic (PK) and biodistribution profiles of Shuttle cell-penetrating peptides (S-CPP) in rodents, combined or not with an immunoglobulin G (IgG) cargo. We compared two enantiomers of S-CPP that contain both a protein transduction domain and an endosomal escape domain, with previously shown capacity for cytoplasmic delivery. The plasma concentration versus time curve of both radiolabelled S-CPPs required a two-compartment PK analytical model, which showed a fast distribution phase (t1/2α ranging from 1.25 to 3 min) followed by a slower elimination phase (t1/2β ranging from 5 to 15 h) after intravenous injection. Cargo IgG combined to S-CPPs displayed longer elimination half-life, of up to 25 h. The fast decrease in plasma concentration of S-CPPs was associated with an accumulation in target organs assessed at 1 and 5 h post-injection, particularly in the liver. In addition, in situ cerebral perfusion (ISCP) of L-S-CPP yielded a brain uptake coefficient of 7.2 ± 1.1 µl g−1 s−1, consistent with penetration across the blood–brain barrier (BBB), without damaging its integrity in vivo. No sign of peripheral toxicity was detected either by examining hematologic and biochemical blood parameters, or by measuring cytokine levels in plasma. In conclusion, S-CPPs are promising non-toxic transport vectors for improved tissue distribution of drug cargos in vivo.

Giant Cell Osteoclast-Like Bladder Carcinoma: A Case Report

Introduction: Osteoclast-like giant cell bladder carcinomas are an extremely unusual and aggressive histological subtype of urothelial carcinomas. Only 30 cases have been reported globally. Clinical case: A 79-year-old male patient was presented to our Urology Department due to macroscopic hematuria that persisted for six months. As part of his diagnostic protocol, a CT scan of the abdomen and pelvis with elimination phase was performed, finding a filling defect of 12 mm at the level of the posterior wall of the bladder. A cystoscopy was subsequently performed, confirming the presence of a 1.5 cm bladder tumor, which was resected in its entirety. Pathology analysis with hematoxylin and eosin stain revealed a composition of mononuclear cells and osteoclast-like giant cells. Immunohistochemistry was positive for epithelial markers cytokeratins AE1/AE3, EMA, P53, and CD68. Conclusion: Osteoclast-like giant cell bladder carcinomas are extremely unusual and aggressive. The only diagnostic method is through immunohistochemistry, confirming the presence of epithelial markers for urothelium in the neoplastic cells. Radical surgical treatment is recommended and there has been no proven effective adjuvant treatment to date. The patients’ median survival is 15 months.

Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [177Lu]Lu-DOTATATE Treatment.

Bone marrow suppression is a common side effect after [177Lu]Lu-DOTATATE treatment of neuroendocrine neoplasms. Neuroendocrine neoplasms share expression of somatostatin receptor type 2 with CD34-positive hematopoietic progenitor cells, potentially leading to active uptake in the radiosensitive red marrow region where these cells are located. This study aimed to identify and quantify specific red marrow uptake using SPECT/CT images collected after the first treatment cycle. Methods: Seventeen patients diagnosed with neuroendocrine neoplasms were treated with [177Lu]Lu-DOTATATE. Seven of them had confirmed bone metastases. After the first treatment cycle, each patient went through 4 SPECT/CT imaging sessions 4, 24, 48, and 168 h after administration. Monte Carlo-based reconstructions were used to quantify activity concentrations in tumors and multiple skeletal sites presumed to house red marrow: the T9-L5 vertebrae and the ilium portion of the hip bones. The activity concentration from the descending aorta was used as input in a compartment model intended to establish a pure red marrow biodistribution by separating the nonspecific blood-based contribution from the specific activity concentration in red marrow. The biodistributions from the compartment model were used to perform red marrow dosimetry at each skeletal site. Results: Increased uptake of [177Lu]Lu-DOTATATE was observed in the T9-L5 vertebrae and hip bones in all 17 patients compared with activity concentrations in the aorta. The mean specific red marrow uptake was 49% (range, 0%-93%) higher than the nonspecific uptake. The median (±SD) total absorbed dose to the red marrow was 0.056 ± 0.023 Gy/GBq and 0.043 ± 0.022 Gy/GBq for the mean of all vertebrae and hip bones, respectively. The patients with bone metastases had an absorbed dose of 0.085 ± 0.046 Gy/GBq and 0.069 ± 0.033 Gy/GBq for the vertebrae and hip bones, respectively. The red marrow elimination phase was statistically slower in patients with fast tumor elimination, which is in line with transferrin transport of 177Lu back to the red marrow. Conclusion: Our results suggest that specific red marrow uptake of [177Lu]Lu-DOTATATE is in line with observations of somatostatin receptor type 2-expressing hematopoietic progenitor cells within the bone marrow. Blood-based dosimetry methods fail to account for the prolonged elimination of specific uptake and underestimate the absorbed dose to red marrow.

Introduction of an electrochemical point-of-care assay for quantitative determination of paracetamol in finger-prick capillary whole blood samples.

Measuring venous plasma paracetamol concentrations is time- and resource-consuming. We aimed to validate a novel electrochemical point-of-care (POC) assay for rapid paracetamol concentration determinations. Twelve healthy volunteers received 1 g oral paracetamol, and its concentrations were analysed 10 times over 12 h for capillary whole blood (POC), venous plasma (high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)), and dried capillary blood (HPLC-MS/MS). At concentrations >30 μM, POC showed upward biases of 20% (95% limits of agreement [LOA] -22 to 62) and 7% (95% LOA -23 to 38) compared with venous plasma and capillary blood HPLC-MS/MS, respectively. There were no significant differences between mean concentrations for the paracetamol elimination phase. Upward biases in POC compared with venous plasma HPLC-MS/MS were likely due to higher paracetamol concentrations in capillary blood than in venous plasma and to faulty individual sensors. The novel POC method is a promising tool for paracetamol concentration analysis.

Elimination Resistance: Characterizing Multi-compartment Toxicokinetics of the Neonicotinoid Thiacloprid in the Amphipod Gammarus pulex Using Bioconcentration and Receptor-Binding Assays.

Delayed toxicity is a phenomenon observed for aquatic invertebrates exposed to nicotinic acetylcholine receptor (nAChR) agonists, such as neonicotinoids. Furthermore, recent studies have described an incomplete elimination of neonicotinoids by exposed amphipods. However, a mechanistic link between receptor binding and toxicokinetic modeling has not been demonstrated yet. The elimination of the neonicotinoid thiacloprid in the freshwater amphipod Gammarus pulex was studied in several toxicokinetic exposure experiments, complemented with in vitro and in vivo receptor-binding assays. Based on the results, a two-compartment model was developed to predict the uptake and elimination kinetics of thiacloprid in G. pulex. An incomplete elimination of thiacloprid, independent of elimination phase duration, exposure concentrations, and pulses, was observed. Additionally, the receptor-binding assays indicated irreversible binding of thiacloprid to the nAChRs. Accordingly, a toxicokinetic-receptor model consisting of a structural and a membrane protein (including nAChRs) compartment was developed. The model successfully predicted internal thiacloprid concentrations across various experiments. Our results help in understanding the delayed toxic and receptor-mediated effects toward arthropods caused by neonicotinoids. Furthermore, the results suggest that more awareness toward long-term toxic effects of irreversible receptor binding is needed in a regulatory context. The developed model supports the future toxicokinetic assessment of receptor-binding contaminants.

The Pioneering Study of Mass Drug Administration with Primaquine in Iran

Background: Mass drug administration (MDA) is considered one of the World Health Organization’s (WHO) global strategies to eliminate malaria. Therefore, the impact of this achievement on reducing malaria transmission should be measured. Objectives: This study aimed to assess the role of MDA with primaquine (PQ) in Jask County, southern Iran. Methods: PQ was chosen as an antimalarial drug for this purpose; then, 168 Pakistani cases receiving MDA were examined from September to December 2021 (for eight weeks) in the Lirdaf district of Jask County, Hormozgan province, southern Iran. Results: Three asymptomatic vivax malaria carriers were detected. Thirty out of 168 people treated with PQ were excluded from the study considering that 26 had glucose-6-plosphate dehydrogenase (G6PD) deficiency. Three people were eliminated from the project, one due to family problems and the other two due to access constraints. One person, who was positive and also asymptomatic at the beginning of the study, became positive again, so this case was disregarded from the survey. All cases were followed up routinely, and interestingly, no relapse was observed in our target population. Conclusions: We suggest that MDA be implemented in the elimination phase associated with other interventions.

Knowledge, attitudes, and practices (KAP) during the malaria elimination phase: A household-based cross-sectional survey.

Malaria is a major health problem in Southwestern Saudi Arabia. This study aimed to measure the level of community understanding of malaria transmission, protection, and treatment. A questionnaire-based cross-sectional study enrolled 1070 participants from 2 districts with different malaria prevalence rates in Jazan Province. The response rate was 97.27%. Of the 1070 total; 754 (70.5%) had heard about malaria. Sixty-seven percentage know that fever was the main symptom. Approximately 59.8% did not know that stagnant water is one of the most important locations for mosquito breeding. Nevertheless, we found that 50% of the participants knew that mosquitoes bite at night and 96.9% confirmed that mosquitoes did not bite during the day. The most effective sources of information were distributed leaflets (41.8%) and video awareness (31.9%). The most significant factors affecting participants knowledge were gender, residence, family members, income, and education (P < .05). Knowledge levels were satisfactory in this study, and the majority of participants exhibited adequate attitudes and practices related to malaria prevention. However, knowledge differences were observed with regard to the place of residence. Greater emphasis should be directed towards education programs in malaria-endemic areas to ensure complete eradication of malaria.

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation.

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0-24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½β, and the first-order rate constant for the elimination process β in FN compared to non-FN patients. Furthermore, AUC0-24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0-24, which may require specific consideration during the treatment initiation.

Optimal designs for a non-linear model for the pharmacokinetics of ethanol elimination in the human body

The equation most commonly used to estimate a person’s blood alcohol concentration after consuming alcoholic drinks assumes zero-order kinetics in the ethanol elimination phase. This implies that the elimination process occurs in the body at a uniform rate as a function of the ethyl-oxidation constant. The model, formulated by Widmark, does not consider the phase of increase in concentration, and approximates the phase of elimination in a linear way, which may be insufficient if the tests are carried out in the first phases of alcohol intake. In this paper, a non-linear model that fits the different phases of the pharmacokinetic process of ethanol in the human body (absorption, distribution, metabolism, and elimination) is proposed. Optimal experimental designs methods are used in order to find the most informative observation times for the estimation of the parameters of the model.