Concurrent Use of Tobacco and Cannabis and Internalizing and Externalizing Problems in US Youths.

Importance: Little is known about whether concurrent use of tobacco and cannabis is associated with higher or lower levels of mental health problems than use of either substance alone among youths. Objective: To examine the association between concurrent use of tobacco and cannabis and mental health problems in a national sample of US youths. Design, Setting, and Participants: This cross-sectional study analyzed publicly available wave 6 data within the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative cohort study of US youths aged 14 to 17 years, collected from March to November 2021. This analysis used wave 6 single-wave weights to obtain statistically valid estimates for cross-sectional analyses generalizable to the wave 4 cohort sample. Data were analyzed from November 15, 2023, to April 20, 2024. Exposure: Past 30-day use of any tobacco and cannabis products was self-reported and categorized into 4 exclusive patterns: concurrent, tobacco only, cannabis only, and nonuse. Main Outcomes and Measures: Self-reported past-year internalizing and externalizing mental health problems were measured using the modified version of the Global Appraisal of Individual Needs-Short Screener and separately categorized into 3 levels: low (0-1 symptoms), moderate (2-3 symptoms), and high (≥4 symptoms). Results: A total of 5585 youths were included in the study, with a weighted proportion of 51.3% being male and 72.5% aged 15 to 17 years. In terms of race and ethnicity, 1606 youths (25.7%) were Hispanic, 626 (12.7%) were non-Hispanic Black, 2481 (50.5%) were non-Hispanic White, and 555 (11.0%) were non-Hispanic other. The prevalence of concurrent use (3.4% [95% CI, 2.9%-4.0%]) was comparable to tobacco-only use (3.9% [95% CI, 3.2%-4.6%]), but greater than cannabis-only use (2.5% [95% CI, 2.1%-2.9%]). High levels of internalizing and externalizing problems were most common for the concurrent use group (internalizing: 47.4% [95% CI, 39.2%-55.9%]; externalizing: 61.6% [95% CI, 54.1%-68.7%]), followed by the cannabis-only use group (internalizing: 44.8% [95% CI, 35.7%-54.1%]; externalizing: 48.5% [95% CI, 39.1%-57.9%]), the tobacco-only use group (internalizing: 41.4% [95% CI, 33.7%-49.5%]; externalizing: 46.3% [95% CI, 38.3%-54.5%]), and the nonuse group (internalizing: 22.4% [95% CI, 21.1%-23.8%]; externalizing: 30.4% [95% CI, 28.9%-31.9%]). After controlling for covariates in ordinal logistic regression models, concurrent use of tobacco and cannabis was associated with greater odds of reporting higher levels of externalizing problems compared with tobacco-only use (adjusted odds ratio [AOR], 1.83 [95% CI, 1.15-2.91]) and cannabis-only use (AOR, 1.85 [95% CI, 1.11-3.06]). However, there were no statistically significant differences in the odds of internalizing problems between concurrent use and use of tobacco or cannabis alone. Conclusions and Relevance: In this cross-sectional study of the PATH Study wave 6 youth data, concurrent use of tobacco and cannabis was linked to higher levels of externalizing mental health problems than use of single substances, indicating a potential need to combine mental health support with tobacco and cannabis cessation interventions for youths.

Association between E-Cigarette Advertising Exposure and Use of E-Cigarettes among a Cohort of U.S. Youth and Young Adults.

Youth and young adult (YYA) use of e-cigarettes increased rapidly between 2010 and 2019 in the United States, during which exposure to e-cigarette advertising was also increased. We aimed to examine whether exposure to e-cigarette advertising among YYAs may lead to subsequent e-cigarette use. A cohort of 3886 YYAs ages 13-24 was recruited from two survey panels in 2018 and followed up until 2019. Survey data were collected online and by telephone. The primary outcome was past 30-day use of e-cigarettes at the follow-up survey. Among 2304 YYAs who retained at the follow-up survey and were not past 30-day e-cigarette users at baseline, both youth and young adults exposed to e-cigarette advertising at baseline had elevated odds of past 30-day e-cigarette use at follow-up (Youth adjusted odds ratio (aOR): 2.77, 95% CI: 1.23, 6.24; Young adults aOR: 2.34, 95% CI: 1.08, 5.11) compared with those not reporting baseline advertising exposure. The majority of YYAs reported exposure to e-cigarette advertising at baseline (Youth: 63.7%, 95% CI: 59.8, 67.4; Young adults: 58.3%, 95% CI: 53.6, 62.8). Our findings suggest that exposure to e-cigarette advertising was associated with an increase in subsequent past 30-day use of e-cigarettes among YYAs. Restricting advertising targeted at YYAs may reduce the likelihood of e-cigarette use among YYAs.

Associations between COVID-19 risk perceptions and smoking and quitting behavior among U.S. adults.

OBJECTIVES: The COVID-19 pandemic may impact cigarette smokers' behaviors. Among smokers, perceptions about the risks of contracting COVID-19 and the severity of COVID-19 illness likely vary, and perceptions may be associated with individual smoking behavior. Our study measured smokers' perceptions of COVID-19 risks and their association with smoking and quitting outcomes. METHODS: A sample of 1,223 U.S. adult cigarette smokers participated in an online survey in October-November 2020 to assess their COVID-19-related risk perceptions and changes in smoking, readiness to quit, and quit attempts during the COVID-19 pandemic. RESULTS: More smokers believed smoking could increase the severity of COVID-19 (43.6%, 95% CI: 40.1, 47.3) than believed smoking makes them more susceptible to COVID-19 (20.0%, 95% CI: 17.2, 23.0.). While there were no associations between perceptions of COVID-19 susceptibility and smoking behaviors or intentions, perceptions of greater smoking-related COVID-19 severity were associated with both higher likelihood of smoking increases (aOR: 2.16, 95% CI: 1.19, 3.93) and greater readiness to quit smoking (aOR: 1.65, 95% CI: 1.18, 2.30). Greater perceptions of general COVID-19 severity were associated with higher likelihood of smoking reductions (aOR: 1.12, 95% CI: 1.02, 1.22), greater readiness to quit smoking (aOR: 1.14, 95% CI: 1.07, 1.22), and higher likelihood of making a quit attempt (aOR: 1.12, 95% CI: 1.04, 1.22). CONCLUSIONS: Smokers' perceptions about COVID-19 severity are related to their smoking behavior and likelihood of making a quit attempt. Providing smokers with accurate information on the relationship between smoking and the severity of COVID-19 may alter smoking behaviors.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.

Prevalence of Diabetes and Prediabetes among Children Aged 11-14 Years Old in Vietnam.

AIM: Diabetes in children is becoming more prevalent in some countries. However, in most countries, little is known about the epidemiology of this disease. This study is aimed at estimating the prevalence of type 1 and type 2 diabetes and prediabetes among children in Vietnam and examining factors associated with the conditions. METHODS: A total of 2880 students aged 11-14 years old were recruited for the survey, using a school-based and nationally representative sampling frame. Capillary blood samples of participants were collected to measure fasting glucose level, using glucose meter OneTouch Verio Pro+. Diabetes and impaired fasting plasma glucose were initially diagnosed based on the cut-off points of the American Diabetes Association criteria. Diabetes status and type of diabetes of participants were confirmed at a hospital. Additionally, anthropometric and blood pressure measurements were conducted following a standardized procedure. Multivariate logistic regression was used to examine the association between outcome and independent variables. RESULTS: The overall prevalence of diabetes among the participants was 1.04‰ (three cases), with 2 cases (0.75‰) diagnosed with type 1 diabetes (one known and one newly diagnosed) and 1 case newly diagnosed with type 2 diabetes (0.35‰). The prevalence of impaired fasting glucose was 6.1%. Body mass index, place of residence, and age were found to be significantly associated with the impaired fasting glucose condition in participants. CONCLUSION: The prevalence of type 1 and type 2 diabetes in children in Vietnam is lower than that in some other countries reported recently. However, there is a high prevalence in impaired fasting glucose, requiring attention from policymakers to take action to prevent the occurrence of the epidemic of type 2 diabetes in children in the future.

Position Statement on Atopic Dermatitis in Sub-Saharan Africa: current status and roadmap.

BACKGROUND: The first International Society of Atopic Dermatitis (ISAD) global meeting dedicated to atopic dermatitis (AD) in Sub-Saharan Africa (SSA) was held in Geneva, Switzerland in April 2019. A total of 30 participants were present at the meeting, including those from 17 SSA countries, representatives of the World Health Organization (WHO), the International Foundation for Dermatology (IFD) (a committee of the International League of Dermatological Societies, ILDS www.ilds.org), the Fondation pour la Dermatite Atopique, as well as specialists in telemedicine, artificial intelligence and therapeutic patient education (TPE). RESULTS: AD is one of the most prevalent chronic inflammatory skin diseases in SSA. Besides neglected tropical diseases (NTDs) with a dermatological presentation, AD requires closer attention from the WHO and national Departments of Health. CONCLUSIONS: A roadmap has been defined with top priorities such as access to essential medicines and devices for AD care, in particular emollients, better education of primary healthcare workers for adequate triage (e.g. better educational materials for skin diseases in pigmented skin generally and AD in particular, especially targeted to Africa), involvement of traditional healers and to a certain extent also patient education, bearing in mind the barriers to effective healthcare faced in SSA countries such as travel distances to health facilities, limited resources and the lack of dermatological expertise. In addition, several initiatives concerning AD research in SSA were discussed and should be implemented in close collaboration with the WHO and assessed at follow-up meetings, in particular, at the next ISAD meeting in Seoul, South Korea and African Society of Dermatology and Venereology (ASDV) meeting in Nairobi, Kenya, both in 2020.

Draft Genome Sequence of a Canine Uropathogenic Escherichia coli Strain Isolated in New Zealand.

Escherichia coli P50 is a canine uropathogenic isolate sampled in the Wellington region of New Zealand. We report the draft genome sequence of this isolate, which contains characteristic virulence genes for urinary tract infections and is predicted to be capable of causing human infections.

Adaptive beam control techniques for airborne free-space optical communication systems.

In this paper, we study two adaptive beam control techniques, where the beam divergence angle is adjusted at the transmitter to (i) maximize link availability or (ii) minimize transmitter power while maintaining target link availability. For this purpose, we provide closed-form expressions about the link availability and optimum beam divergence angle under the effect of generalized two-dimensional Gaussian distribution of the alignment error between the transmitter and receiver. These simple and closed-form expressions reduce the computational complexity for performance optimization. Thus, they can be used to (i) reduce the power consumption required for adaptive beam control and (ii) facilitate the fast operation of the control techniques. The results show that the adaptive beam control techniques can improve system performance under various scenarios.

Duplex PCR assay and in situ hybridization for detection of Francisella spp. and Francisella noatunensis subsp. orientalis in red tilapia.

Conventional isolation and identification based on phenotypic characteristics is challenging with the highly fastidious, intracellular bacterium Francisella noatunensis subsp. orientalis (Fno). Here, we developed a duplex PCR method for simultaneous detection of the Francisella genus and Fno in one PCR reaction and an in situ hybridization method for paraffin section based diagnosis of Fno. The PCR results showed genus- and species-specific bands (1140 and 203 bp) from Fno but only one genus-specific band (1140 bp) from F. noatunensis subsp. noatunensis. Sensitivity of the duplex PCR assay revealed a detection limit of 20 to 200 fg genomic DNA (~10 to 100 genome equivalents) depending on DNA template extraction methods. The newly developed duplex PCR assay could be used to detect Fno from clinically sick fish exhibiting signs of visceral granulomas and would also be able to detect Fno infection in naturally diseased fish without symptoms of francisellosis, indicating potential application for diagnosis of field samples. The in situ hybridization assay using Fno species-specific probe revealed positive signals in multiple organs including the spleen, liver, kidney, gills and intestine of infected fish.

Dermatomyositis: factors predicting relapse.

BACKGROUND: The course of dermatomyositis (DM) can be chronic with relapses, which are associated with major morbidity. OBJECTIVE: The aim of this study was to identify presentation features that predict DM relapses. METHODS: We retrospectively reviewed data of patients with DM recorded from 1990 to 2011, including muscle biopsy results. Characteristics of patients with and without relapses were compared. Hazard ratios (HRs) were estimated using a Cox model. RESULTS: We identified 34 patients, with a mean age of 46 ± 17 years (range, 18-77) and 24 (71%) women. The muscle and skin abnormalities relapsed in 21 (61%) patients. By univariate analysis, two presentation features were significantly associated with a subsequently relapsing course, namely, dysphonia [HR = 3.2 (1.2-8.5)] and greater skin lesion severity defined as a Cutaneous Disease Area Severity Index [CDASI] > 20 [HR = 3.5 (1.2-7.9)]. CONCLUSION: Dysphonia and skin lesion severity at disease onset must be recorded, as they significantly predict a relapsing disease course.

[Cutaneous revelation of Rosai-Dorfman disease: 7 cases]. / Maladie de Rosai-Dorfman à révélation cutanée: 7 observations.

BACKGROUND: Rosai-Dorfman disease (RDD) is a benign form of non-Langerhans-cell histiocytosis. It is identified by a particular histological profile first observed in febrile lymph nodes. Extranodal sites are frequent. The most common site is the skin, which can reveal the disease despite a difficult and delayed diagnosis. Seven cases of cutaneous revelation of RDD were studied retrospectively in order to delineate the clinical characteristics and facilitate diagnosis and treatment of this extremely rare disease. PATIENTS AND METHODS: Six cases of RDD from 1990 to 2011 were identified in the photographic and histopathological records of the Saint-Louis Hospital and one case came from a Bichat Hospital consultation. The diagnosis was based in all cases on histopathology results. RESULTS: Patients consisted of four men and three women aged between 31 and 69 years. Cutaneous lesions (3 to 20) revealed the disease in all of them and the time from disease onset to diagnosis ranged from six months to five years. The clinical presentation was erythematous or orange popular nodules or plaques, usually on the face. Microscopically, a dense dermal infiltration was observed, in some cases extending into the subcutaneous tissue, with pale histiocytic cells characterised by emperipolesis, plasma cells, lymphocytes, some neutrophils and variable fibrosis. The diagnosis, initially erroneous in 4 cases, was rectified by a second reading of histopathology slides, and immunohistochemical studies showed expression of S-100 protein in histiocytes but not CD1a. Three patients had pure cutaneous RDD. Two neurological sites and one nasal site were also found, with one ENT site and sequelae of previous uveitis in one patient. All extra-cutaneous sites were identified by clinical examination. Different treatments were proposed according to the sites and impact of the disease. In one case, the lesions regressed spontaneously after 18 months. COMMENTS: Few RDD series have been published and they mainly concern Asian patients. The ethnic origin of our patients was varied. The main findings were: 1) common clinical findings (orange or erythematous papules or nodules, mostly on the upper body), which should alert the dermatologist and histopathologist to the possible diagnosis of RRD; 2) the possibility, already mentioned in the literature, of spontaneous regression and a good prognosis; 3) the need for thorough evaluation by thoracic, abdominal and cerebral CT (computed tomography) or more a PET (positron emission tomography) scan to screen for potentially dangerous visceral sites, and also clinical follow up.

Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma.

OBJECTIVE: We sought to investigate whether intrapleural topical application of cisplatin with a surgical carrier has a prolonged local tissue level in comparison with cisplatin solution while reducing systemic toxicity. METHODS: Forty immune-competent Fischer rats were inoculated with 10(6) mesothelioma cells. Ten days later, left pneumonectomy with tumor debulking was performed. Twenty animals underwent local application of cisplatin solution (100 mg/m2), whereas the same quantity of cisplatin was topically applied as a gel with the Vivostat (Vivolution) system in 20 other animals. In each group 5 subgroups of 4 animals were defined according to the harvesting time of blood and tissue samples (2, 4, 24, and 72 hours and 1 week) after local therapy. Platinum concentrations in serum and tissue and systemic toxicity were analyzed. RESULTS: Platinum concentrations in tissue were significantly higher in the gel group (group 1) than in the solution group (group 2) at 1, 3, and 7 days after therapy (1510, 1224, and 1069 pg/mg for group 1 vs 598, 382, and 287 pg/mg for group 2; P = .007, P = .005, and P = .0002, respectively). Laboratory findings showed renal insufficiency in the animals of the solution group at 1 week, with values of 98 mmol/L versus 7.7 mmol/L for urea and 410 mumol/L versus 43 mumol/L for creatinine (P = .02 and P = .01, respectively), which was confirmed by means of pathologic analysis. CONCLUSIONS: Intrapleural administration of cisplatin with the carrier Vivostat significantly provides sustained higher platinum concentrations up to 1 week in tissue in comparison with application of cisplatin solution without conferring systemic toxicity in this model.

Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation.

Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect. A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system. Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1-1 ng ml(-1)). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent. Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3. Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.

Signal transduction inhibitors as radiosensitizers.

DNA double strand breaks are the pivotal cellular damage induced by ionizing radiation. A plethora of molecular and cellular processes are activated as part of the cellular stress response that result in cell cycle arrest and induction of the DNA-repair machinery to restore the damage of DNA or to activate a cell death program. However ionizing radiation also initiates signal transduction cascades that are generated at cellular sites distant from and independent of DNA-damage. These signaling processes are similar to hormone activated growth factor receptor controlled signal transduction cascades and represent interesting targets for anticancer treatment modalities combining ionizing radiation with molecular defined pharmacological compounds. Activation of these signal transduction cascades upon irradiation or upregulation of growth factor mediated pathways due to oncogene-transformation often contribute to an acquired or inherent treatment resistance in malignant cells. Therefore pharmacological compounds inhibiting specific key-entities of these signal transduction cascades potentially sensitize for radiation induced cell death. Here we describe current preclinical concepts of combined treatment strategies with locoregional-applied ionizing radiation and molecular defined signal transduction inhibitors to overcome a high treatment threshold in tumor cells.

Effect of VEGF receptor inhibitor PTK787/ZK222584 [correction of ZK222548] combined with ionizing radiation on endothelial cells and tumour growth.

The vascular endothelial growth factor (VEGF) receptor is a major target for anti-angiogenesis-based cancer treatment. Here we report the treatment effect of ionizing radiation in combination with the novel orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 on endothelial cell proliferation in vitro and with tumour xenografts in vivo. Combined treatment of human umbilical vein endothelial cells with increasing doses of PTK787/ZK222584 and ionizing radiation abrogated VEGF-dependent proliferation in a dose-dependent way, but inhibition of endothelial cell proliferation was not due to apoptosis induction. In vivo, a combined treatment regimen of PTK787/ZK222584 (4 x 100 mg/kg) during 4 consecutive days in combination with ionizing radiation (4 x 3 Gy) exerted a substantial tumour growth delay for radiation-resistant p53-dysfunctional tumour xenografts derived from SW480 colon adenocarcinoma cells while each treatment modality alone had only a minimal effect on tumour size and neovascularization. SW480 tumours from animals that received a combined treatment regimen, displayed not only an extended tumour growth delay but also a significant decrease in the number of microvessels in the tumour xenograft. These results support the model of a cooperative anti-tumoral effect of angiogenesis inhibitor and irradiation and show that the orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 is suitable for combination therapy with irradiation.

Lack of influence of gender on outcomes of mechanically ventilated medical ICU patients.

STUDY OBJECTIVES: Recent studies combining medical and surgical patients have suggested that mortality is higher for mechanically ventilated women than for men. This study was designed to determine whether there are gender-based differences in outcomes in mechanically ventilated medical ICU (MICU) patients. DESIGN AND SETTING: Prospective observational study in an MICU of a tertiary-care academic medical center. PATIENTS: Five hundred eighty consecutive patients admitted to the MICU service and mechanically ventilated for a minimum of 12 h. RESULTS: There was no difference in overall hospital mortality rate (woman, 36.3%; men, 40.4%; p > 0.2). No differences in mortality rates were noted after stratification based on age, underlying comorbid condition, APACHE (acute physiology and chronic health evaluation) II score, indication for mechanical ventilation, or acute hepatic or renal failure. Using a multiple logistic regression model, gender was not independently associated with hospital mortality. No differences were found between men and women for a number of secondary outcomes, including likelihood of undergoing weaning trials, success of weaning trials, time between onset of mechanical ventilation and extubation, total time on mechanical ventilation, rate of unplanned extubations, need for reintubation or tracheostomy, or duration of MICU and hospital stay, after the onset of mechanical ventilation. The number and timing of orders written to withhold care were comparable between men and women. CONCLUSIONS: Using univariate and multivariate analyses, we found no differences in hospital mortality rates between mechanically ventilated men and women. Differences in the process of care or gender-based treatment bias may explain previously reported differences in outcomes.

A pharmacokinetic and pharmacodynamic study of artesunate for vivax malaria.

To investigate the pharmacokinetic and pharmacodynamic properties of artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) in Plasmodium vivax infections, 12 male Vietnamese adults with slide-positive vivax malaria received either intravenous ARTS (120 mg; group 1) or oral ARTS (100 mg; group 2) with the alternative preparation given 8 hr later in a randomized, open, cross-over study. Following intravenous injection, ARTS had a peak plasma drug concentration (Cmax) of 35.6 microM (13.7 mg/L), an elimination half-life (t1/2) of 2.2 min, a clearance (CL) of 3.0 L/hr/kg, and a volume of distribution (V) of 0.16 L/kg. Dihydroartemisinin had a Cmax of 7.7 microM (2.2 mg/L), a tmax of 8 min, a t1/2 of 37 min, an apparent CL of 1.1 L/hr/kg, and an apparent V of 0.9 L/kg. Following oral ARTS, the mean relative bioavailability of DHA was 85%, the Cmax was 3.0 microM (0.85 mg/L), the tmax was 75 min, and t1/2 was 40 min. The mean time to 50% reduction in the parasite count (PCT50) and median fever clearance time were 3 hr and 16 hr, respectively. Following intravenous ARTS (group 1), the PCT50 for total parasites, rings, trophozoites, and gametocytes was 3.3 hr, 3.2 hr, 4.0 hr, and 3.6 hr, respectively. This study confirms that ARTS is effective against P. vivax, with rapid clearance of sexual and asexual forms of the parasite. Artesunate is a suitable initial treatment for vivax malaria, or when the plasmodial species cannot be reliably identified.