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2.
Pediatr Res ; 95(3): 668-678, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37500755

RESUMO

BACKGROUND: Very preterm infants are at elevated risk for neurodevelopmental delays. Earlier prediction of delays allows timelier intervention and improved outcomes. Machine learning (ML) was used to predict mental and psychomotor delay at 25 months. METHODS: We applied RandomForest classifier to data from 1109 very preterm infants recruited over 20 years. ML selected key predictors from 52 perinatal and 16 longitudinal variables (1-22 mo assessments). SHapley Additive exPlanations provided model interpretability. RESULTS: Balanced accuracy with perinatal variables was 62%/61% (mental/psychomotor). Top predictors of mental and psychomotor delay overlapped and included: birth year, days in hospital, antenatal MgSO4, days intubated, birth weight, abnormal cranial ultrasound, gestational age, mom's age and education, and intrauterine growth restriction. Highest balanced accuracy was achieved with 19-month follow-up scores and perinatal variables (72%/73%). CONCLUSIONS: Combining perinatal and longitudinal data, ML modeling predicted 24 month mental/psychomotor delay in very preterm infants ½ year early, allowing intervention to start that much sooner. Modeling using only perinatal features fell short of clinical application. Birth year's importance reflected a linear decline in predicting delay as birth year became more recent. IMPACT: Combining perinatal and longitudinal data, ML modeling was able to predict 24 month mental/psychomotor delay in very preterm infants ½ year early (25% of their lives) potentially advancing implementation of intervention services. Although cognitive/verbal and fine/gross motor delays require separate interventions, in very preterm infants there is substantial overlap in the risk factors that can be used to predict these delays. Birth year has an important effect on ML prediction of delay in very preterm infants, with those born more recently (1989-2009) being increasing less likely to be delayed, perhaps reflecting advances in medical practice.


Assuntos
Doenças do Recém-Nascido , Transtornos das Habilidades Motoras , Lactente , Humanos , Recém-Nascido , Feminino , Gravidez , Recém-Nascido Prematuro , Idade Gestacional , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Retardo do Crescimento Fetal
3.
Heliyon ; 9(11): e21274, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027850

RESUMO

In this study, the conversion of monosaccharides to 5-hydroxymethylfurfural (5-HMF) using different deep eutectic solvents (DESs) was investigated in various conditions. Among all the investigated DESs, [ChCl][trichloroacetic acid], based on choline chloride and trichloroacetic acid with the ratio 1:1, showed the highest catalytic activity. A maximum 5-HMF yield was 82 % for 1 h at 100 °C using [ChCl][trichloroacetic acid] as a catalyst from fructose. [ChCl][trichloroacetic acid] could be recovered and reused three times with a slight loss in activity. Our work demonstrated the low-cost and effective method for the synthesis of 5-HMF from carbohydrates.

4.
Genome Biol Evol ; 15(5)2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37079743

RESUMO

Humans have had a major influence on the dissemination of crops beyond their native range, thereby offering new hybridization opportunities. Characterizing admixed genomes with mosaic origins generates valuable insight into the adaptive history of crops and the impact on current varietal diversity. We applied the ELAI tool-an efficient local ancestry inference method based on a two-layer hidden Markov model to track segments of wild origin in cultivated accessions in the case of multiway admixtures. Source populations-which may actually be limited and partially admixed-must be generally specified when using such inference models. We thus developed a framework to identify local ancestry with admixed source populations. Using sequencing data for wild and cultivated Coffea canephora (commonly called Robusta), our approach was found to be highly efficient and accurate on simulated hybrids. Application of the method to assess elite Robusta varieties from Vietnam led to the identification of an accession derived from a likely backcross between two genetic groups from the Congo Basin and the western coastal region of Central Africa. Admixtures resulting from crop hybridization and diffusion could thus lead to the generation of elite high-yielding varieties. Our methods should be widely applicable to gain insight into the role of hybridization during plant and animal evolutionary history.


Assuntos
Coffea , Café , Humanos , Animais , Coffea/genética , Mapeamento Cromossômico , Genoma de Planta , Software , Produtos Agrícolas/genética
5.
Am J Health Syst Pharm ; 80(17): 1147-1156, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37052227

RESUMO

PURPOSE: This research was conducted to evaluate the influence of a pharmacy residency candidate's prior work or research experience on the potential for selection for an interview. Additionally, residency program directors (RPDs) were asked to evaluate the importance of letters of intent and recommendation, rank the importance of typical curriculum vitae (CV) items along with general preferences, and provide advice for a standout CV. METHODS: This cross-sectional, survey-based study recruited RPDs to review a work-focused or research-focused fictitious residency candidate CV and complete a 33-question survey regarding interest in interviewing the fictitious candidate and their general perceptions of significant factors in interview candidate selection. RESULTS: A total of 456 RPDs responded to the survey, with 229 respondents assigned to evaluate the work-focused CV and 227 assigned to review the research-focused CV. Among RPDs who provided CV evaluations, 81.2% (147/181) of those who reviewed the research-focused CV and 78.3% (137/175) of those who reviewed the work-focused CV gave a positive evaluation (P > 0.05). Work experience and extracurricular activities were considered the most important CV sections, and high-quality advanced pharmacy practice experience (APPE) rotations and pharmacy work experience were perceived to have the highest correlation with success in residency. CONCLUSION: This work supports the importance of candidates creating a well-rounded CV in preparing themselves for residency. Pharmacy-related work experience and high-quality APPE rotations seem to be key in an RPD's opinions of predicted success in a residency program. The CV remains a vital document in the residency candidate review process, and it deserves a high degree of effort in ensuring it adequately reflects professional experiences.


Assuntos
Internato e Residência , Residências em Farmácia , Farmácia , Humanos , Estudos Transversais , Seleção de Pessoal
6.
RSC Adv ; 13(11): 7257-7266, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36891489

RESUMO

In this study, three carbon-based solid acid catalysts were prepared via the one-step hydrothermal procedure using glucose and Brønsted acid, including sulfuric acid, p-toluenesulfonic acid, or hydrochloric acid. The as-synthesized catalysts were tested for their ability to convert cellulose into valuable chemicals. The effects of Brønsted acidic catalyst, catalyst loading, solvent, temperature, time, and reactor on the reaction were investigated. The as-synthesized C-H2SO4 catalyst containing Brønsted acid sites (-SO3H, -OH, and -COOH functional groups) demonstrated high activity in the transformation of cellulose into valuable chemicals with the yield of total products of 88.17% including 49.79% LA in 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) solvent at 120 °C in 24 h. The recyclability and stability of C-H2SO4 were also observed. A proposed mechanism of cellulose conversion into valuable chemicals in the presence of C-H2SO4 was presented. The current method could provide a feasible approach for the conversion of cellulose into valuable chemicals.

7.
Mhealth ; 9: 3, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36760784

RESUMO

Background: Mobile health (mHealth) has been used to promote sexual and reproductive health (SRH) education and services; however, little is known about the use of mHealth to improve safe abortion knowledge and access to safe abortion services among female sex workers (FSWs). This study evaluated the feasibility and effectiveness of iConnect intervention through changes in knowledge on safe abortion and changes in perceived barriers to safe abortion services among FSWs in Vietnam. Methods: iConnect mobile app was developed as an interactive platform to deliver safe abortion education and referral to safe abortion services through short messaging services (SMS) enhanced by tele-counseling for 512 FSWs in Hanoi, Vietnam. A pretest-posttest evaluation was conducted using questionnaire-based phone interviews administered to 251 participants at baseline and 3 months following the intervention. Non-parametric tests evaluated the change in abortion knowledge, behaviors, and perceived barriers to safe abortion. Results: There were significant improvements in the knowledge on safe abortion among the study participants. Specifically, FSWs' knowledge of correct gestational ages (≤22 weeks) for medical abortion increased from 78.9% at baseline to 96.8% (P=0.001). Knowledge of correct gestational ages for medical abortion at the private clinic increased from 45.3% to 63.1% (P=0.001). Knowledge on the consequences of unsafe abortion increased from 75.2% to 92.1% (P=0.001). In addition, perceived stigma and discrimination when seeking safe abortion decreased from 36.5% to 27.8% (P=0.036) and worry about the lack of confidentiality decreased from 23.3% to 15.5% (P=0.035). Conclusions: The evaluation results showed the initial effectiveness of a mobile app-based intervention in improving access to safe abortion information and services among FSWs. A future study is needed to establish the efficacy of the intervention for scaling up in Vietnam and elsewhere.

8.
PNAS Nexus ; 2(2): pgac315, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36798622

RESUMO

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3 to 4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.

9.
Front Integr Neurosci ; 17: 1251252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38344668

RESUMO

Neurodevelopmental disorders are on the rise, yet their average diagnosis is after 4.5 years old. This delay is partly due to reliance on social-communication criteria, which require longer maturation than scaffolding elements of neuromotor control. Much earlier criteria could include reflexes, monitoring of the quality of spontaneous movements from central pattern generators and maturation of intentional movements and their overall sensation. General Movement Assessment (GMA) studies these features using observational means, but the last two decades have seen a surge in digital tools that enable non-invasive, continuous tracking of infants' spontaneous movements. Despite their importance, these tools are not yet broadly used. In this work, using CiteSpace, VOSViewer and SciMAT software, we investigate the evolution of the literature on GMA and the methods in use today, to estimate how digital techniques are being adopted. To that end, we created maps of key word co-occurrence networks, co-author networks, document co-citation analysis and strategic diagrams of 295 publications based on a search in the Web of Science, Dimensions and SCOPUS databases for: 'general movement assessment' OR 'general movements assessment'. The nodes on the maps were categorized by size, cluster groups and year of publication. We found that the state-of-the-art methodology to diagnose neurodevelopmental disorders still relies heavily on observation. Several groups in classical GMA research have branched out to incorporate new techniques, but few groups have adopted digital means. We report on additional analyses of methods and biosensors usage and propose that combining traditional clinical observation criteria with digital means may allow earlier diagnoses and interventional therapies for infants.

10.
Nat Biomed Eng ; 6(8): 979-991, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35986185

RESUMO

Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects two Mycobacterium tuberculosis virulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study. It also distinguished tuberculosis from latent-tuberculosis infections in non-human primates. We adapted the assay to make it portable and operable by a smartphone. With further development, the assay may facilitate the detection of tuberculosis at the point of care, particularly in resource-limited settings.


Assuntos
Vesículas Extracelulares , Mycobacterium tuberculosis , Tuberculose , Animais , Estudos de Coortes , Humanos , Tuberculose/diagnóstico , Fatores de Virulência
11.
J Pediatr Pharmacol Ther ; 27(4): 306-311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558342

RESUMO

OBJECTIVE: Vitamin D deficiency is commonly found in patients with cystic fibrosis (CF) and can have a negative effect on patients who are not at target goal according to Cystic Fibrosis Foundation's Vitamin D Deficiency Clinical Care Guidelines. The objective of this study is to determine the effectiveness of a pharmacist-driven vitamin D protocol (PDVDP) in improving, achieving, and maintaining 25-hydroxyvitamin D levels of patients in a pediatric CF clinic. METHODS: A retrospective chart review was conducted for pediatric patients with CF from August 2018 to March 2020 to determine the percent of patients with improvement in 25-hydroxyvitamin D levels to target goal (≥ 30 ng/mL). Patients' 25-hydroxyvitamin D levels at 6, 12, and 18 months after automatic enrollment into the PDVDP were compared to determine if improvement occurred, and to calculate relative percent increase of 25-hydroxyvitamin D levels for these patients. RESULTS: The mean 25-hydroxyvitamin D levels of the patients at baseline before the protocol and 6, 12, and 18 months after enrollment in the protocol were 23.2, 33.3, 32.7, and 34.6 ng/mL, respectively. These results demonstrate mean 25-hydroxyvitamin D levels at all follow-up time points were significantly greater than baseline (p < 0.001). At 6 months, 50% (n = 20) of pediatric patients reached the target 25-hydroxyvitamin D levels. CONCLUSIONS: The PDVDP was effective in increasing the number of patients able to reach target 25-hydroxyvitamin D levels. Our PDVDP process may also be used at other CF clinics to improve vitamin D outcomes collaboratively with the interprofessional CF team.

12.
Commun Biol ; 5(1): 480, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35590096

RESUMO

Mycobacterium tuberculosis (Mtb) is responsible for approximately 1.5 million deaths each year. Though 10% of patients develop tuberculosis (TB) after infection, 90% of these infections are latent. Further, mice are nearly uniformly susceptible to Mtb but their M1-polarized macrophages (M1-MΦs) can inhibit Mtb in vitro, suggesting that M1-MΦs may be able to regulate anti-TB immunity. We sought to determine whether human MΦ heterogeneity contributes to TB immunity. Here we show that IFN-γ-programmed M1-MΦs degrade Mtb through increased expression of innate immunity regulatory genes (Inregs). In contrast, IL-4-programmed M2-polarized MΦs (M2-MΦs) are permissive for Mtb proliferation and exhibit reduced Inregs expression. M1-MΦs and M2-MΦs express pro- and anti-inflammatory cytokine-chemokines, respectively, and M1-MΦs show nitric oxide and autophagy-dependent degradation of Mtb, leading to increased antigen presentation to T cells through an ATG-RAB7-cathepsin pathway. Despite Mtb infection, M1-MΦs show increased histone acetylation at the ATG5 promoter and pro-autophagy phenotypes, while increased histone deacetylases lead to decreased autophagy in M2-MΦs. Finally, Mtb-infected neonatal macaques express human Inregs in their lymph nodes and macrophages, suggesting that M1 and M2 phenotypes can mediate immunity to TB in both humans and macaques. We conclude that human MФ subsets show unique patterns of gene expression that enable differential control of TB after infection. These genes could serve as targets for diagnosis and immunotherapy of TB.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Citocinas/genética , Citocinas/metabolismo , Humanos , Imunidade Inata/genética , Macrófagos/metabolismo , Camundongos , Tuberculose/metabolismo
13.
Emerg Infect Dis ; 28(3): 582-590, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35195518

RESUMO

Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts.


Assuntos
Emigrantes e Imigrantes , Tuberculose Latente , Feminino , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Estudos Prospectivos , Teste Tuberculínico , Estados Unidos/epidemiologia
14.
Cardiovasc Endocrinol Metab ; 10(4): 210-214, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34765891

RESUMO

The ankle-brachial index (ABI) is a fast, simple, noninvasive method that provides accurate results in the early diagnosis of peripheral artery disease. Microalbuminuria is considered a predictor of renal and cardiovascular complications in patients with diabetes. This study was conducted to determine the correlation between ABI and microalbuminuria with certain risk factors in patients with type 2 diabetes. SUBJECTS AND RESEARCH METHODS: A cross-sectional descriptive study was performed on 62 inpatients with type 2 diabetes. All patients were measured for ABI as well as microalbuminuria, HbA1c, glucose and lipidemia in the blood. RESULTS: The study results showed that in patients with dyslipidemia, the risk of having microalbuminuria (+) increased 5.7 times and ABI ≤0.90 increased 8.6 times (P = 0.004 and 0.021, respectively). Fasting blood glucose >7.2 mmol/L had 5.7 times higher microalbuminuria (+) risk and 8.6 times higher ABI ≤0.90 (P = 0.004 and 0.021, respectively). Patients with HbA1c ≥7% were 2.9 times more likely to have microalbuminuria (+) and ABI ≤0.90 (P = 0.043 and 0.048, respectively). CONCLUSIONS: Peripheral vascular disease risk factors such as hypertension, dyslipidemia and waist circumference and the effectiveness of fasting blood glucose and HbA1c control increased the risk of high microalbuminuria and ABI in patients with type 2 diabetes.

15.
Am J Respir Crit Care Med ; 204(10): 1211-1221, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34343025

RESUMO

Rationale: The Southeast Asian tuberculosis burden is high, and it remains unclear if urban indoor air pollution in this setting is exacerbating the epidemic. Objectives: To determine the associations of latent tuberculosis with common urban indoor air pollution sources (secondhand smoke, indoor motorcycle emissions, and cooking) in Southeast Asia. Methods: We enrolled child household contacts of patients with microbiologically confirmed active tuberculosis in Vietnam, from July 2017 to December 2019. We tested children for latent tuberculosis and evaluated air pollution exposures with questionnaires and personal aerosol sampling. We tested hypotheses using generalized estimating equations. Measurements and Main Results: We enrolled 72 patients with tuberculosis (27% with cavitary disease) and 109 of their child household contacts. Latent tuberculosis was diagnosed in 58 (53%) household contacts at baseline visit. Children experienced a 2.56-fold increased odds of latent tuberculosis for each additional household member who smoked (95% confidence interval, 1.27-5.16). Odds were highest among children exposed to indoor smokers and children <5 years old exposed to household smokers. Each residential floor above street-level pollution decreased the odds of latent tuberculosis by 36% (adjusted odds ratio, 0.64; 95% confidence interval, 0.42-0.96). Motorcycles parked inside children's homes and cooking with liquid petroleum gas compared with electricity increased the odds of latent tuberculosis, whereas kitchen ventilation decreased the effect, but these findings were not statistically significant. Conclusions: Common urban indoor air pollution sources were associated with increased odds of latent tuberculosis infection in child household contacts of patients with active tuberculosis.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Culinária , Suscetibilidade a Doenças , Tuberculose Latente/induzido quimicamente , Medição de Risco/estatística & dados numéricos , Poluição por Fumaça de Tabaco/efeitos adversos , Emissões de Veículos , Povo Asiático/estatística & dados numéricos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Razão de Chances , População Urbana/estatística & dados numéricos , Vietnã
17.
J Am Pharm Assoc (2003) ; 61(6): e52-e59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34391689

RESUMO

BACKGROUND: Well-being, burnout, and resiliency have been topics of discussion among health care providers over the last few years. Wellness can relate to many areas or domains in our lives such as financial, social, spiritual, physical, and occupational, whereas well-being is career focused. Wellness is multidimensional and encompasses different domains, and well-being usually focuses on a singular domain. Literature supports the study of well-being in health care workers; however, research is limited for assessing wellness in different domains of health care workers. OBJECTIVE: This study sought to describe perceived pharmacy resident wellness during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A 67-item survey was sent by e-mail to eligible study participants, including any postgraduate year (PGY) 1, 2, or 24-month pharmacy resident completing/completed their training in June 2019-July 2020. The primary outcome was perceived resident wellness based on the 7 domains from Princeton UMatter Wellness Self-Assessment, developed to measure self-perceptions of wellness across dimensions. Descriptive statistics and participant scores were aggregated and presented as a total domain score. Statistics and scores were determined from completed surveys. RESULTS: A total of 418 participants accessed the survey, 384 met inclusion criteria, and 326 completed the survey. Of the participants, 77% were female with 85% completing a traditional PGY-1 residency program. The wellness domain with the lowest total was physical wellness, with a domain median of 23 of 28. The highest-scoring domain was social wellness, with a median of 27. CONCLUSION: Perceived resident wellness during COVID-19 was highest in the social domain and lowest in the physical wellness domain. Residency programming administrators could use this information to make improvements to orientation practices and wellness domain programming throughout the duration of residency training during a pandemic.


Assuntos
Esgotamento Profissional , COVID-19 , Internato e Residência , Farmácia , Feminino , Humanos , SARS-CoV-2 , Inquéritos e Questionários
18.
N Engl J Med ; 384(18): 1705-1718, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33951360

RESUMO

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antituberculosos/uso terapêutico , Moxifloxacina/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Intervalos de Confiança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Moxifloxacina/efeitos adversos , Rifampina/efeitos adversos , Adulto Jovem
19.
Nat Commun ; 12(1): 2899, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006838

RESUMO

There is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and regimens vary in treatment-shortening activity, but the molecular basis of these differences is unclear, and no existing assay directly quantifies the ability of a drug or regimen to shorten treatment. Here, we show that drugs historically classified as sterilizing and non-sterilizing have distinct impacts on a fundamental aspect of Mycobacterium tuberculosis physiology: ribosomal RNA (rRNA) synthesis. In culture, in mice, and in human studies, measurement of precursor rRNA reveals that sterilizing drugs and highly effective drug regimens profoundly suppress M. tuberculosis rRNA synthesis, whereas non-sterilizing drugs and weaker regimens do not. The rRNA synthesis ratio provides a readout of drug effect that is orthogonal to traditional measures of bacterial burden. We propose that this metric of drug activity may accelerate the development of shorter TB regimens.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Precursores de RNA/metabolismo , RNA Ribossômico/metabolismo , Tuberculose/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiologia , Precursores de RNA/genética , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Ribossômico/genética , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/microbiologia
20.
Curr Pharm Teach Learn ; 13(6): 705-710, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33867068

RESUMO

INTRODUCTION: The purpose of this analysis was to determine which characteristics increase a candidate's likelihood of matching with a post-graduate year 1 (PGY1) community-based residency program (CBRP). METHODS: Current and former CBRP residents' curriculum vitae (CVs) were collected and reviewed utilizing a survey and standardized rubric. Eligible participants were current PGY1 CBRP residents or had completed a PGY1 program no earlier than 2015. Primary endpoints included number of participants with extensive leadership experience, relevant experiential rotations, presentation history, and involvement in pharmacy organizations. Descriptive statistics were performed to identify the most common characteristics and their relative quantities. RESULTS: A total of 50 eligible CVs were submitted and reviewed. The majority of participants had extensive (defined as four or more) presentation experiences, at least three mid- to high-level leadership experiences, multiple ambulatory/outpatient pharmacy experiential rotations, and involvement in pharmacy organizations. Few participants (26%) had previous teaching experience. CONCLUSIONS: Residency candidates who matched with CBRPs tended to have extensive mid- to high-level leadership experiences and presentation experience. Based on these findings, additional studies are warranted to compare existing and/or redesigned postgraduate training preparation curricula and their impact on residency match rates.


Assuntos
Educação de Pós-Graduação em Farmácia , Internato e Residência , Residências em Farmácia , Estudantes de Farmácia , Humanos
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