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OBJECTIVE: Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment. STUDY DESIGN AND SETTING: We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used. RESULTS: Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase. CONCLUSION: We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.
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Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Duración de la Terapia , Fluoroquinolonas/farmacología , Rifampin/farmacología , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
Objectives: To describe the incidence of venous thromboembolism (VTE) in mechanically ventilated COVID-19 patients in an HIV endemic, resourced constrained setting. To describe the incidence of VTE in relation to HIV status and anticoagulant therapy, and to evaluate VTE-associated cardio-respiratory changes. To establish the contribution of HIV, anticoagulation therapy and other risk factors to mortality. Design: Prospective descriptive study. Setting: Single-center tertiary teaching hospital. Participants: One hundred and one consecutively admitted critically ill adult patients with COVID-19 acute respiratory distress syndrome. Interventions: Point of care ultrasound (POCUS) assessment of the lower limbs and the cardio-respiratory system was performed on intensive care unit (ICU) admission and repeated if clinically indicated. Measurements and main results: DVT was diagnosed by POCUS, whilst pulmonary embolism was diagnosed using a combination of clinical criteria and POCUS (echocardiography and chest wall ultrasound). VTE was diagnosed in 16/101 (16%) patients, despite 14/16 (88%) receiving prior therapeutic dosage of low molecular weight heparin. Clinically significant PE was diagnosed in 5/16 (31%) with 11/16 (69%) having DVT only. The majority of VTE patients, 12/16 (75%), demised 16/101 (16%) patients had HIV co-infection, and 4/16 (25%) with HIV had VTE. Valvular abnormalities were the most common cardiac abnormality with marked tricuspid regurgitation detected in 51/101 (51%). The absence of right atrial enlargement had a 93% negative predictive value for the absence of VTE. Univariate analysis did not demonstrate statistically significant individual risk factors for mortality. Conclusions: Mechanically ventilated COVID- 19 patients at ICU admission had a low incidence of VTE (16%). Therapeutic dose anticoagulation did not reduce mortality compared to prophylactic dosage. In contrast to findings from other studies, no individual risk factor contributed significantly to mortality, likely due to small sample size. POCUS is an ideal screening tool to aid in the assessment of critically ill patients.
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Robotic manipulation refers to how robots intelligently interact with the objects in their surroundings, such as grasping and carrying an object from one place to another. Dexterous manipulating skills enable robots to assist humans in accomplishing various tasks that might be too dangerous or difficult to do. This requires robots to intelligently plan and control the actions of their hands and arms. Object manipulation is a vital skill in several robotic tasks. However, it poses a challenge to robotics. The motivation behind this review paper is to review and analyze the most relevant studies on learning-based object manipulation in clutter. Unlike other reviews, this review paper provides valuable insights into the manipulation of objects using deep reinforcement learning (deep RL) in dense clutter. Various studies are examined by surveying existing literature and investigating various aspects, namely, the intended applications, the techniques applied, the challenges faced by researchers, and the recommendations adopted to overcome these obstacles. In this review, we divide deep RL-based robotic manipulation tasks in cluttered environments into three categories, namely, object removal, assembly and rearrangement, and object retrieval and singulation tasks. We then discuss the challenges and potential prospects of object manipulation in clutter. The findings of this review are intended to assist in establishing important guidelines and directions for academics and researchers in the future.
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Robótica , Humanos , Robótica/métodos , Fuerza de la Mano , Mano , Extremidad SuperiorRESUMEN
Tuberculosis (TB) is an infectious disease that threatens >10 million people annually. Despite advances in TB diagnostics, patients continue to receive an insufficient diagnosis as TB symptoms are not specific. Many existing biodiagnostic tests are slow, have low clinical performance, and can be unsuitable for resource-limited settings. According to the World Health Organization (WHO), a rapid, sputum-free, and cost-effective triage test for real-time detection of TB is urgently needed. This article reports on a new diagnostic pathway enabling a noninvasive, fast, and highly accurate way of detecting TB. The approach relies on TB-specific volatile organic compounds (VOCs) that are detected and quantified from the skin headspace. A specifically designed nanomaterial-based sensors array translates these findings into a point-of-care diagnosis by discriminating between active pulmonary TB patients and controls with sensitivity above 90%. This fulfills the WHO's triage test requirements and poses the potential to become a TB triage test.
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Piel/metabolismo , Tuberculosis/diagnóstico , Tuberculosis/metabolismo , Compuestos Orgánicos Volátiles/metabolismo , Adulto , Biomarcadores/metabolismo , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , India , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sudáfrica , Adulto JovenRESUMEN
New all-oral regimens for rifampin-resistant tuberculosis (RR-TB) are being scaled up globally. Measurement of drug concentrations in hair assesses long-term drug exposure. Delamanid (DLM) is likely to be a key component of future RR-TB treatment regimens, but a method to describe its quantification in hair via liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not previously been described. We developed and validated a simple, fast, sensitive, and accurate LC-MS/MS method for quantifying DLM and its metabolite DM-6705 in small hair samples. We pulverized and extracted two milligrams of hair in methanol at 37 °C for two hours, and diluted 1:1 with water. A gradient elution method eluted DLM, DM-6705, and the internal standard OPC 14714 within 3 min, bringing overall analysis time to 5.5 min. The method has limits of detection (LOD) of 0.0003 ng/mg for DLM and 0.003 ng/mg for DM-6705. The established linear dynamic ranges are 0.003-2.1 ng/mg and 0.03-21 ng/mg for DLM and DM-6705, respectively. Eleven of 12 participant hair samples had concentrations within DLM's linear dynamic range, while all 12 samples had concentrations within the quantifiable range for DM-6705. The ranges of concentrations observed in these clinical samples for DLM and DM-6705 were 0.004-0.264 ng/mg hair and 0.412-12.041 ng/mg hair respectively. We demonstrate that while DLM was detected in hair at very low levels, its primary metabolite DM-6705 had levels approximately 100 times higher. Measuring DM-6705 in hair may accurately reflect long-term adherence to DLM-containing regimens for drug-resistant TB.
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Cromatografía Liquida/métodos , Cabello/química , Nitroimidazoles/análisis , Oxazoles/análisis , Espectrometría de Masas en Tándem/métodos , Humanos , Límite de Detección , Modelos Lineales , Nitroimidazoles/uso terapéutico , Oxazoles/uso terapéutico , Reproducibilidad de los Resultados , Tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
BACKGROUND: Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. METHODS: Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda. RESULTS: Among the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5, 95% confidence interval [CI], 40.7-99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort. CONCLUSIONS: Hair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not known.
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Antituberculosos/análisis , Monitoreo de Drogas/métodos , Cabello/química , Rifampin/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Cromatografía Liquida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem , Tuberculosis/tratamiento farmacológicoAsunto(s)
Antituberculosos/sangre , Linezolid/sangre , Tuberculosis Resistente a Múltiples Medicamentos/sangre , Adulto , Antituberculosos/uso terapéutico , Cromatografía Liquida , Femenino , Humanos , Linezolid/uso terapéutico , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto JovenRESUMEN
Therapeutic drug monitoring for drug-resistant tuberculosis (TB) is likely to improve treatment outcomes. While assessments of plasma drug levels can explain pharmacokinetic variability among trial participants, these measures require phlebotomy and a cold chain, and are generally not repeated frequently enough to characterise drug exposure over time. Using a novel multi-analyte assay, we found evidence that higher anti-TB drug concentrations in hair, a non-biohazardous and noninvasively collected biomatrix, predict extensively-drug resistant-TB clinical outcomes in a high-burden setting.
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PURPOSE: To evaluate the safety and effectiveness of antegrade vs crossover femoral artery access in the endovascular treatment of isolated below-the-knee (BTK) lesions in patients with critical limb ischemia (CLI). METHODS: Between January 2014 and December 2015, 224 high-risk patients (mean age 75.8±9.8 years; 151 men) with CLI underwent infragenicular interventions on 292 crural vessels in 3 European vascular centers. All patients had isolated TransAtlantic Inter-Society Consensus (TASC) C (n=26) or D (n=198) BTK lesions. Primary endpoints were freedom from access-related complications and technical success comparing the antegrade vs crossover access groups. RESULTS: Balloon angioplasty was the most used treatment modality (169 vessels, 75.4%). The technical success rate was 88.4% in the entire cohort and 88.0% in the antegrade group vs 90.4% in the crossover group (p>0.99). In all patients, the technical success rate was higher for stenotic lesions (100%) vs occlusions (85.5%, p=0.002) and in patients with TASC C BTK lesions (100%) vs TASC D (86.9%, p=0.033). The overall freedom from access-related complications was 97.8%: 99% in the antegrade group and 90.6% in the crossover group (p=0.022). Larger sheath size (5/6-F vs 4-F) was associated with a significantly higher risk for access-related complications (7.1% vs 1.1%, respectively; p=0.047). CONCLUSION: The present multicenter study showed high technical success and a low incidence of access-related complications in the treatment of isolated BTK lesions using either antegrade or crossover femoral access. The antegrade approach with the use of a 4-F system seems to have a significantly lower rate of access-related complications.
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Angioplastia de Balón/métodos , Arteria Femoral , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/terapia , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Enfermedad Crítica , Supervivencia sin Enfermedad , Femenino , Arteria Femoral/diagnóstico por imagen , Alemania , Humanos , Isquemia/diagnóstico por imagen , Isquemia/fisiopatología , Italia , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Punciones , Estudios Retrospectivos , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Necrotizing fasciitis (NF) is a life-threatening infectious disease whose incidence has been on the rise. Commonly a consequence of group A beta-hemolytic Streptococcus infection, it results in high levels of morbidity and mortality. Diagnosis is difficult and treatment involves emergent surgical intervention and antibiotic therapy. The aim of this study is to examine the incidence of NF in Manitoba with the goal of observing whether there is a geographic variation in incidence and outcomes based on Regional Health Authorities (RHAs). This is a 6-year retrospective chart review of all NF patients who presented to the Health Sciences Center from 2004 to 2009. A total of 130 patients satisfied the inclusion criteria. The mean age was 47 ± 16 years. The most common comorbidities were diabetes (33.8%) and hypertension (33.1%). The overall mortality was 13.1% with advanced age being an independent risk factor (P < .05). Lower extremity was the most common location of infection (44.6%) and the most common causative organism was group A beta-hemolytic Streptococcus (63.9%). The type of infection (mono- vs. polymicrobial) was not found to affect length of stay, amputation rate, or mortality. There was no statistical difference in rate of amputations, length of stay, or mortality based on RHA. Incidence within the province, however, varied significantly based on RHA and ethnicity (P < .05). We determined that regardless of origin before admission, all our patients have equivalent prognosis. Burntwood RHA was found to have substantially higher incidence than the rest of the province, and higher incidence was established among the Aboriginal population.