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Coronavirus disease 2019 can be indistinguishable from lower respiratory tract infections (LRTIs) caused by other viral and bacterial agents. This likely contributed to antimicrobial use (AU) and antimicrobial resistance (AMR) during the pandemic. Our antimicrobial stewardship program targeted the selection and duration of therapy for LRTIs and led to a reduction in AU and AMR.
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Background: Limited data reporting real-world prevalence of integrase strand transfer inhibitor resistance (INSTI-R) in the USA are available because their recommendation as first-line treatment in 2017. Reported national surveillance data in the USA estimated INSTI-R to be 6.3% as of 2018. This article aims to describe estimated prevalence of INSTI-R within a single clinic network in Chicago, IL, USA, and identify risk factors for resistance and virological failure (VF). Methods: This was a retrospective, single-centre study of adults with HIV starting an INSTI-containing regimen between September 2017 and 2020. The primary endpoint was the difference in INSTI-R of the sample population compared with the national prevalence. Other outcomes included VF and documented INSTI-R mutations. Results: Of 948 participants screened, 321 were included. Eight people had baseline INSTI-R testing results available, of which five had INSTI-R at baseline for an estimated prevalence of 1.6%. This estimation was significantly less than the national estimated prevalence of 6.3% (p<0.001). VF occurred in 26 (7.8%) individuals. Because no participants acquired INSTI-R during the study period, investigators were unable to identify risk factors associated with the development of INSTI-R. People with high pre-treatment viral loads had 1.21 (95% CI 1.05-1.39) higher odds of VF. Conclusions: Amongst participants on INSTI-containing regimens, INSTI-R rates were estimated to be lower than the estimated national prevalence. Detectable pre-switch viral loads were more associated with VF than undetectable viral loads.
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Broad-spectrum antimicrobials are commonly used without indication and contribute to antimicrobial resistance (AMR). We implemented a syndrome-based stewardship intervention in a community hospital that targeted common infectious syndromes and antipseudomonal beta-lactam (APBL) use. Our intervention successfully reduced AMR, C. difficile rates, use of APBLs, and cost.
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P-Delta is a nonlinear phenomenon that results from the consideration of axial loads acting on the deformed configuration of a member of the structure, usually a beam-column. This effect is especially significant in slender members, which can undergo large transversal displacements which tend to increase the bending moment caused by an axial load P acting upon them. The P-delta effect can be computed through a geometrically nonlinear analysis, usually employing the Finite Element Method, which subdivides each bar of the frame in finite segments known as elements. Since discretization (subdivision) and the use of iterative schemes (like Newton-Raphson) are sometimes undesirable, especially for students, avoiding it can be didactically interesting. This work proposes the use of a new approach to perform a simplified nonlinear analysis using the two-cycle method and a tangent stiffness matrix obtained directly from the homogeneous solution of the problem's (beam-column) differential equation. The proposed approach is compared to the results obtained by the traditional two-cycle method which uses geometric and elastic stiffness matrices based on cubic (Hermitian) polynomials and a P-Delta approximation using the pseudo (fictitious) lateral load method.
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The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted Black, indigenous, and people of color (BIPOC). Equitable access to therapeutics is key to addressing health disparities. We established a monoclonal infusion program in the emergency department of a safety-net hospital. Our program successfully reached underserved BIPOC communities and was sustained throughout the pandemic.
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Anticorpos Monoclonais , COVID-19 , Humanos , Anticorpos Monoclonais/uso terapêutico , COVID-19/terapia , Serviço Hospitalar de Emergência , Estudos de Viabilidade , Pandemias/prevenção & controle , Populações Vulneráveis , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à SaúdeRESUMO
COVID-19 therapies were challenging to deploy due to evolving literature and conflicting guidelines. Antimicrobial stewardship can help optimize drug use. We conducted a survey to understand the role of stewardship and formulary restrictions during the pandemic. Restrictions for COVID-19 therapies were common and approval by infectious disease physicians often required.
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Deploying therapeutics for coronavirus disease 2019 (COVID-19) has proved challenging due to evolving evidence, supply shortages, and conflicting guideline recommendations. We conducted a survey on remdesivir use and the role of stewardship. Use differs significantly from guidelines. Hospitals with remdesivir restrictions were more guideline concordant. Formulary restrictions can be important for pandemic response.
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Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed.
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As antimicrobial resistance continues to grow, one of the biggest threats includes the members of the Enterobacterales order presenting with carbapenem resistance (CRE). Meropenem-vaborbactam, along with other beta-lactam/beta-lactamase agents, has been developed to help combat this growing concern and is currently approved to treat complicated urinary tract infections (cUTI), as well as acute pyelonephritis (AP), in the USA. Vaborbactam is a novel beta-lactamase inhibitor designed specifically to optimize and restore the activity of meropenem against resistant Enterobacterales. Vaborbactam inhibits a number of beta-lactamases, including in vitro activity against extended-spectrum beta-lactamases (ESBL) and the Klebsiella pneumoniae carbapenemase (KPC) group. KPC represents one of the most clinically relevant carbapenemase in the USA, accounting for the majority of carbapenemase-producing CRE. Meropenem-vaborbactam has been studied in the two Phase 3, noninferiority trials, TANGO I and TANGO II. TANGO I compared meropenem-vaborbactam against piperacillin-tazobactam in patients with cUTIs and was found to be noninferior for overall success and microbial eradication. TANGO II expanded to other disease states (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia [HAP/VAP], complicated intra-abdominal infection [cIAI], cUTI/AP) and was found to be noninferior against best available therapy (BAT) with respect to clinical cure at the end of treatment and the test of cure. Meropenem-vaborbactam maintained the established safety profile of meropenem alone, with headache as the most common adverse event in both phase 3 studies. Overall, clinical efficacy has been demonstrated and suggests the use of meropenem-vaborbactam for the treatment of cUTI is an option.
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Deploying novel COVID-19 therapies proved challenging amid rapidly evolving data, drug shortages, and conflicting guidelines. We established a remdesivir formulary restriction remdesivir to promote its evidence-based use. This intervention led to changes in remdesivir utilization patterns and cost savings. Formulary restrictions can play an important role in pandemic preparedness and response.
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ABSTRACT Objective This study aims to estimate the epidemiological burden of excessive salt intake reduction and achieve the World Health Organization salt reduction target for 2025 in Paraguay, in 2019. Methods We used the Preventable Risk Integrated Model, a comparative risk assessment macro-simulation model, to estimate the averted deaths, disease incidence, and disability-adjusted life years from cardiovascular disease attributable to salt intake in the population of Paraguay for different salt reduction policy scenarios. Results As a result, in Paraguay, excessive salt intake (over 5 g/day) is responsible for approximately 2,656 cardiovascular disease deaths (95% Uncertainty Interval: 1,250-3,765), 4,816 cardiovascular disease cases (95% UI: 2,251-6,947), and 60,529 disability-adjusted life years (95% UI: 27,828-86,258) per year. By reducing salt consumption by 30%, as recommended by the World Health Organization until 2025, approximately 1,188 deaths (95% UI: 520 to 1,820), 2,100 incident cases (95% UI: 923-3,234), and 27,272 disability-adjusted life years (95% UI: 11,999-41,675) from cardiovascular disease could be averted every year. Conclusion In conclusion, the burden of cardiovascular disease attributable to excessive salt intake is significant and salt reduction policies must become a priority in Paraguay.
RESUMO Objetivo Este estudo visa estimar a carga epidemiológica do consumo excessivo de sal e o alcance da meta da Organização Mundial de Saúde para 2025 no Paraguai, em 2019. Métodos Foi usado um modelo de avaliação comparativa de risco (Preventable Risk Integrated Model) para análise comparativa de risco para estimar mortes, casos incidentes e anos de vida ajustados por incapacidade (DALYs) por doenças cardiovasculares atribuíveis ao consumo excessivo de sal na população paraguaia em diferentes cenários. Resultados No Paraguai, o consumo excessivo de sal é responsável por aproximadamente 2.656 mortes (Intervalo de Incerteza 95%: 1.250-3.765), 4.816 casos incidentes (95% II: 2.251-6.947) e 60.529 DALYs (95% II: 27.828-86.258) por doenças cardiovasculares por ano. Com uma redução de 30% no consumo de sal, como recomendado pela Organização Mundial de Saúde até 2025, aproximadamente 1.188 mortes (95% II: 520-1.820), 2.100 casos incidentes (95% II: 923-3.234) e 27.272 DALYs (95% II: 11.999-41.675) por doenças cardiovasculares poderiam ser prevenidos ou adiados por ano. Conclusão Concluiu-se que a carga de doenças cardiovasculares atribuível ao consumo excessivo de sal no Paraguai é significante e políticas de redução deveriam ser priorizadas no país.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Sódio na Dieta/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Cloreto de Sódio na Dieta/análise , Paraguai , Organização Mundial da Saúde , Mortalidade/etnologia , Cloreto de Sódio na Dieta/efeitos adversos , Política de Saúde , Hipertensão/mortalidadeRESUMO
Introducción: Para la contención de la pandemia causada por la enfermedad del coronavirus (COVID-19) se aplicaron una serie de medidas sanitarias a toda la población, como el distanciamiento social, cierre de fronteras y cuarentena en el hogar. Dichas medidas, además, pudieron haber repercutido en un deterioro de la salud en general, un aumento del consumo de bebidas alcohólicas y otras sustancias para contrarrestar o reducir la intensidad de su respuesta a estas consecuencias. Objetivo: Determinar las características demográficas del consumo de riesgo para alcohol durante el tiempo de cuarentena estricta por la pandemia de covid-19. Metodología: Estudio observacional analítico de corte transverso tipo exploratorio. Constó de 16.538 encuestas virtuales realizadas a personas mayores de edad pertenecientes a todo el territorio nacional entre junio y septiembre del 2020. Se excluyó a 219 encuestados por no cumplir criterios de inclusión o datos incorrectamente llenados. Se determinó el consumo de riesgo mediante una prueba que calificaba el consumo por puntajes. Más de 5 puntos para hombres, más de 4 para mujeres. Resultados: 12224 participantes adultos (18-65 años) con una media de 31,9 años (±9,2), formaron parte del análisis, con predominio de participación masculina 64,5% (n=10531). El 74,9% (n=12224) proveniente del Eje Metropolitano. Según géneros, el OR fue 1,15 IC95 (1,08 - 1,23), vp=0,001. Al comparar nivel educativo, secundaria completa/incompleta, el OR fue 1,56 IC95 (1,19 - 2,06), vp=0,001. Y al comparar por ejes de residencias el OR fue 0,83 IC95 (0,77 - 0,89), vp=0,001. Discusión: Se pudo observar que, durante el tiempo de cuarentena, el consumo de alcohol crecía conforme el nivel educativo de la población aumentaba. Los hombres presentaron un consumo de riesgo mayor que los hombres. Conocer este comportamiento ayudaría a plantear acciones que ayuden a prevenir el consumo de alcohol en el grupo de mayor riesgo.
Introduction: The impact of the outbreak of pandemic proportions of COVID-19 has initiated several health and social measures worldwide. Thus, there is growing concern about the consequences of preventive social confinement associated with the pandemic due to the potential increase in the consumption of alcohol and other harmful substances. Between 2010-2014, in Paraguay approximately 5% of deaths over 15 years of age are attributable to alcohol consumption and are associated with external cause injuries, cancers, liver disease, cardiovascular diseases, addictions and domestic violence. Early detection and treatment are recommended intervention strategies to prevent these consequences. Objective: To determine the demographic characteristics of alcohol risk consumption during the covid-19 pandemic quarantine period. Methods: Analytical cross-sectional, exploratory observational study. It consisted of 16,538 virtual surveys carried out on persons of legal age throughout the national territory between June and September 2020. A total of 219 respondents were excluded for not meeting the inclusion criteria or for incorrectly filled out data. Risk consumption was determined using a test that rated consumption by scores. More than 5 points for men, more than 4 for women. Results: 12224 adult participants (18-65 years old) with a mean age of 31.9 years (±9.2), were part of the analysis, with a predominance of male participation 64.5% (n=10531). The 74.9% (n=12224) came from the Metropolitan Axis. According to gender, the OR was 1.15 CI95 (1.08 - 1.23), pv=0.001. When comparing educational level, high school complete/incomplete, the OR was 1.56 CI95 (1.19 - 2.06), pv=0.001. And when comparing by axes of residence, the OR was 0.83 CI95 (0.77 - 0.89), pv=0.001. Discussion: It was observed that, during the quarantine period, alcohol consumption increased as the educational level of the population increased. Males presented a higher risk consumption than males. Knowing this behavior would help to propose actions to help prevent alcohol consumption in the most at-risk group.
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Although tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have been evaluated in various clinical trials, limited safety and efficacy data exist in real-world settings. The goal of this retrospective analysis is to assess changes in virological suppression, immunological status, renal function, weight and body mass index (BMI) amongst people living with HIV who switched from a TDF-based to a TAF-based regimen. Of 130 patients included in the final analysis, 53 patients experienced an increase in their viral load upon switching from TDF to TAF therapy whilst 62 patients remained undetectable. For those who experienced a viral blip, 33 (62%) resuppressed by the time of last follow-up, 15 (28%) patients did not have additional labs beyond the last follow-up and concern for failure occurred in 5 (9%) patients. No differences in immunological function, renal function, weight or BMI were observed from before switching to the last follow-up. Although a loss of virological suppression was found upon switching to TAF at subsequent follow-up visits, resuppression ultimately occurred in most patients.
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The unprecedented toll of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus 2019 disease (COVID-19), jumpstarted the race towards the development and distribution of effective treatment and prevention options. With an urgent need to slow viral transmission, lessen disease severity, and reduce mortality, biopharmaceutical companies rapidly began investigating potential COVID-19 vaccinations. While typical vaccine development can take upwards of 10-15 years, COVID-19 vaccines were developed in less than a year after the identification of COVID-19. To accomplish this feat, clinical development, manufacturing scale-up and distribution are occurring in parallel for the four COVID-19 vaccine front-runners. This remarkable opportunity will forever change the drug development process and would not be possible without tremendous dedication from the public and private sectors, researchers, and clinical trial volunteers. However, many challenges still lie ahead. Comprehensive plans for equitable vaccine education, distribution, administration and post-marketing surveillance must be implemented successfully to overcome vaccine hesitancy, supply-chain obstacles and healthcare provider shortages in an already overburdened healthcare system. We are moving forward at a remarkable pace but worldwide immunity through vaccination will take time to achieve. Thus, current prevention efforts of masking, hand hygiene and social distancing must remain in effect for the foreseeable future. We must remain diligent and not fatigue in our efforts. Ending the COVID-19 pandemic cannot rest on the promise of vaccination alone - it will require a continued, robust and multi-faceted approach to disease treatment and prevention.
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This paper presents a unified method developed by Rodrigues et al. [1] to obtain a complete tangent stiffness matrix for spatial geometric nonlinear analysis using minimal discretization. The formulation presents four distinct important aspects to a complete analysis: interpolation (shape) functions, higher-order terms in the strain tensor and in the finite rotations, an updated Lagrangian kinematic description, and shear deformation effect (Timoshenko beam theory). Thus, the tangent stiffness matrix is calculated from the differential equation solution of deformed infinitesimal element equilibrium, considering the axial load and the shear deformation in this relation. This solution provides interpolation functions that are used in an updated Lagrangian formulation to construct the spatial tangent stiffness matrix considering higher-order terms in the strain tensor and in the finite rotations. The method provides an efficient formulation to perform geometric nonlinear analyses and predict the critical buckling load for spatial structures with moderate slenderness and with the interaction between axial and torsion effects, considering just one element in each member or a reduced discretization.â¢Complete expressions for a geometric nonlinear analyses considering one element per memberâ¢Spatial analyses considering higher-order terms in the strain tensor and large rotationsâ¢Shear deformation influence included.
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BACKGROUND: Persons with human immunodeficiency virus (HIV) experience high rates of medication-related errors when admitted to the inpatient setting. Data are lacking on the impact of a combined antiretroviral (ARV) stewardship and transitions of care (TOC) program. We investigated the impact of a pharmacist-driven ARV stewardship and TOC program in persons with HIV. METHODS: This was a retrospective, quasi-experimental analysis evaluating the impact of an HIV-trained clinical pharmacist on hospitalized persons with HIV. Patients included in the study were adults following up, or planning to follow up, at the University of Illinois (UI) outpatient clinics for HIV care and admitted to the University of Illinois Hospital. Data were collected between July 1, 2017 and December 31, 2017 for the preimplementation phase and between July 1, 2018 and December 31, 2018 for the postimplementation phase. Primary and secondary endpoints included medication error rates related to antiretroviral therapy (ART) and opportunistic infection (OI) medications, all-cause readmission rates, medication access at time of hospital discharge, and linkage to care rates. RESULTS: A total of 128 patients were included in the study: 60 in the preimplementation phase and 68 in the postimplementation phase. After the implementation of this program, medication error rates associated with ART and OI medications decreased from 17% (10 of 60) to 6% (4 of 68) (P = .051), 30-day all-cause readmission rates decreased significantly from 27% (16 of 60) to 12% (8 of 68) (P = .03), and linkage to care rates increased significantly from 78% (46 of 59) to 92% (61 of 66) (P = .02). CONCLUSIONS: A pharmacist-led ARV stewardship and TOC program improved overall care of persons with HIV through reduction in medication error rates, all-cause readmission rates, and an improvement in linkage to care rates.
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BACKGROUND: Drug-induced liver injury (DILI) is a rare but known adverse event associated with trimethoprim-sulfamethoxazole (TMP-SMX) in adults. No studies to date have looked at the risk of this association in children. We systematically reviewed the evidence for a potential association between TMP-SMX and DILI in the pediatric population. METHODS: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Scopus and Web of Science was searched using a combination of terms to identify reports of TMP-SMX exposure, liver injury and pediatrics (≤18 years old). We included any studies with hepatic adverse events occurring after exposure to TMP-SMX. Bibliographies were reviewed for additional relevant references. The Narajno scale was used to assess causality in case studies. RESULTS: A total of 22 studies were identified: 3 randomized trials, 1 prospective observational study, 8 retrospective observational studies and 10 case reports. Among the randomized trials and prospective studies, only mild, transient hepatic function abnormalities were reported. Retrospective observational studies reported 1 fatal DILI and statistically significant increased odds of DILI with TMP-SMX use compared with nonuse. Among the 10 case reports, severe liver outcomes and mild hepatic function abnormalities were both reported. Naranjo scores suggested reported hepatic adverse events were probably because of exposure in 5, possible in 4, and doubtful in 1 case report. CONCLUSIONS: Evidence regarding DILI associated with TMP-SMX exposure in pediatrics is limited. Observational population studies show mild hepatic abnormalities. Case reports suggest more severe manifestations of DILI. Additional studies may reveal the association between TMP-SMX and DILI in pediatrics.
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Antibacterianos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Humanos , Fígado/efeitos dos fármacos , Fígado/microbiologia , Fígado/patologia , Estudos Observacionais como Assunto , Pediatria , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos RetrospectivosRESUMO
RESUMEN Introducción: La obesidad en niños se asocia también a ingesta de alimentos ricos en grasas, azúcares y sodio, por ello es importante conocer sus niveles en golosinas y las bebidas dulces. Objetivos: Evaluar contenido de nutrientes críticos acorde al Perfil de Nutrientes de OPS en golosinas dulces, snacks salados y bebidas dulces no alcohólicas envasadas, según información del etiquetado nutricional. Materiales y Métodos: Estudio transversal, descriptivo, exploratorios. Se evaluó contenido por porción de grasas totales(GT), saturadas(GS) y trans(GTr), sodio, azúcares libres(AL) y edulcorantes artificiales(EA) en golosinas dulces, saladas, y bebidas dulces no alcohólicas (BDNA) según etiquetado nutricional. Niveles excesivos fueron considerados según "Perfil de nutrientes de OPS". Muestra fue por conveniencia obtenida en 2 bocas de expendio. Se excluyeron postres envasados y golosinas con información poco visible. Resultados: Fueron evaluados 104 alimentos agrupados en: confitería (alfajor, magdalenas), chocolates, snacks salados (queso, maíz, galletitas saladas, papas fritas), galletitas dulces, bebidas dulces (jugos/gaseosas/bebidadeportistas). En confitería, 8/13 tenían exceso de GT, 10/13 de GS, 4/13 de GTr, 11/13, de AL, ninguno exceso de sodio, 11/13 tenían EA. Entre chocolates, todos tenían exceso de GT y GS, 2/10 en GTr, ninguno sodio, 9/10 altos en AL, 2/10 contenían EA. Snacks:, 14/17 eran altos en GT, 7/17 en GS, 1/17 en GTr, 15/17 en sodio, 4/17 en AL, 6/17 contenían EA. Galletitas dulces tenían exceso de GT 14/20, de GS 17/20, 6/20 de GTr, de sodio 1/20, todos con AL,17/20 contenían EA. En BDH (n=44), todas tenían exceso de sodio, 36/44 exceso de AL, 21/44 tenían EA. Conclusión: Alimentos de confitería son altos en grasas, azúcares libres y edulcorantes.. Los chocolates son altos en grasas y azucares. Los snacks son altos en sodio y grasas. Las galletitas tienen exceso de azúcares y grasas saturadas, 2/3 contienen edulcorantes artificiales. Las bebidas dulces son altas en sodio y azucares, la mitad tiene edulcorantes artificiales.
ABSTRACT Introduction: Obesity in children is also associated with intake of foods high in fat, sugar and sodium, so it is important to know their levels in sweets and sweet drinks. Objectives: To evaluate critical nutrient content according to the PAHO Nutrient Profile in sweet treats, salty snacks and packaged non-alcoholic sweet drinks, according to nutritional labeling information. Materials and Methods: This was a cross-sectional, descriptive, exploratory study. Content per serving of total fat (TF), saturated fats (SF) and trans-fatty acids (TrF), sodium, free sugars (FS) and artificial sweeteners (AS) in sweet, salty, and non-alcoholic sweet drinks (NASD) was evaluated according to nutritional labeling. Excessive levels were considered according to the "PAHO Nutrient Profile". Samples were obtained for convenience at two outlet stores. Packaged desserts and treats with poorly visible information were excluded. Results: We evaluated 104 foods, which were grouped in: baked foods (alfajor, muffins), chocolates, salty snacks (cheese, corn, crackers, french fries), sweet cookies, and sweet drinks (juices / soft drinks / sports drinks). In baked foods, 8/13 had excess of TF, 10/13 of SF, 4/13 of TrF, 11/13 of FS, no excess of sodium, 11/13 had AS. Among chocolates, all had excess of TF and SF, 2/10 in TrF, none of sodium, 9/10 were high in FS, 2/10 contained AS. Snacks: 14/17 were high in TF, 7/17 in SF, 1/17 in TrF, 15/17 in sodium, 4/17 in FS, 6/17 contained AS. Sweet cookies had excess TF (14/20), SF (17/20), 6/20 had excess of TrF, sodium (1/20), all had excess FS, 17/20 contained AS. In NASD (n = 44), all had excess sodium, 36/44 had excess FS, 21/44 had AS. Conclusion: Baked foods are high in fat, free sugars and sweeteners. Chocolates are high in fats and sugars. Snacks are high in sodium and fat. Cookies have excess sugar and saturated fat, 2/3 contained artificial sweeteners. Sweet drinks are high in sodium and sugars, half have artificial sweeteners.
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Omadacycline is a novel aminomethylcycline antibiotic (antibacterial). Omadacycline has had chemical structure modifications at the C9 and C7 positions of the core tetracycline rings that allow stability in the efflux pump and ribosomal protection protein mechanisms of tetracycline resistance. The systemic exposure (i.e., maximum plasma concentrations [Cmax] and area under the plasma concentration-time curve [AUC]) after intravenous (IV) administration were linear and predictable over the dose range of 25 and 600 mg in healthy subjects. The oral bioavailability of omadacycline was 34.5% under fasted conditions (no food intake 6 h before and 4 h after dosing). Both AUC and Cmax values significantly decreased (41-61%) when a high-fat meal, with and without dairy, were administered 2 h before oral dosing of omadacycline. Similar to other tetracyclines, it is advisable to avoid concurrent administration of divalent- or trivalent cation-containing products (e.g., antacids and iron-containing preparations) for at least 4 h after oral administration of omadacycline. Omadacycline has a large volume of distribution (190 L) and low plasma protein binding (21.3%) that was concentration independent. Systemic exposure of omadacycline in epithelial lining fluid (ELF) and alveolar macrophages was greater than in plasma in healthy adult subjects. Omadacycline is excreted unchanged in the feces (81.1%) and urine (14.4%), and has a low potential for drug-drug interactions since it was not a substrate, inhibitor, or inducer of major cytochrome-metabolizing enzymes or organic anion transporters (OATs). No clinically significant differences in the pharmacokinetics of omadacycline have been observed for age, sex, and renal or hepatic impairment. Pharmacokinetic-pharmacodynamic studies have confirmed that the AUC from time zero to 24 h (AUC24)/minimum inhibitory concentration (MIC) ratio was the best index for correlating unbound plasma and total-drug ELF concentrations with the efficacy of omadacycline. A population pharmacokinetic model was developed with data from healthy subjects and infected patients and used to establish interpretive criteria for in vitro susceptibility testing and dosing regimens of omadacycline for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia.
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Bactérias/efeitos dos fármacos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Tetraciclinas/farmacocinética , Administração Intravenosa , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Antibacterianos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Interações Medicamentosas/fisiologia , Feminino , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tetraciclinas/sangueRESUMO
Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.