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1.
Eur J Vasc Endovasc Surg ; 67(3): 490-498, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37633444

RESUMEN

OBJECTIVE: Early clot removal using endovascular intervention aims to reduce post-thrombotic syndrome (PTS) following iliofemoral deep venous thrombosis (DVT). This may reduce long term morbidity but incurs a higher initial cost. This study examined the cost effectiveness of catheter directed thrombolysis (CDT) and pharmacochemical thrombectomy (PMT) compared with oral anticoagulation (OAC) alone for treatment of acute iliofemoral DVT in the United Kingdom. METHODS: A combined decision tree (acute DVT complications) and Markov model (long term complications [PTS]) was used for decision analytic modelling with five states: no PTS, mild PTS, moderate PTS, severe PTS, and dead. All patients started with acute DVT. Patients who survived acute complications transitioned into the Markov model. Cycle time was six months. A healthcare payer perspective and lifetime horizon was used, adjusting for excess mortality due to history of thrombosis. Data for probabilities, transition probabilities, mortality, and utilities were obtained from the published literature. Cost data were obtained from UK NHS tariffs and published literature. Outcomes were mean lifetime cost, quality adjusted life years (QALYs), and cost effectiveness. RESULTS: Over a patient's lifetime, OAC was more costly (£37 206) than CDT (£32 043) and PMT (£36 288). Mean lifetime QALYs for OAC (12.9) were lower than CDT (13.5) and PMT (13.3). Therefore, in the incremental cost effectiveness analysis, both CDT and PMT were dominant: CDT was less costly (-£5 163) and more effective (+0.6 QALYs) than OAC, and PMT was also less costly (-£917) and more effective (+0.3 QALYs) than OAC. Results were robust to univariable sensitivity analyses, but probabilistic sensitivity analyses suggested considerable parameter uncertainty. CONCLUSION: Early interventional treatment of iliofemoral DVT is cost effective in the UK. Future clinical and epidemiological studies are needed to characterise parameter uncertainty. Further analysis of modern practice, alternative treatments, and optimised care models is warranted.


Asunto(s)
Síndrome Postrombótico , Trombosis de la Vena , Humanos , Terapia Trombolítica/efectos adversos , Análisis de Costo-Efectividad , Resultado del Tratamiento , Trombosis de la Vena/terapia , Trombectomía/efectos adversos , Síndrome Postrombótico/etiología , Enfermedad Aguda , Vena Ilíaca/cirugía
2.
BMC Pregnancy Childbirth ; 21(1): 292, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33838663

RESUMEN

BACKGROUND: India has the highest number of stillbirths and the highest neonatal death rate in the world. In the context of its pronatalist society, women who experience perinatal loss often encounter significant social repercussions on top of grief. Furthermore, even when pregnancy outcomes were favorable, adverse life circumstances put some women at risk for postnatal depression. Therefore, perinatal loss and postnatal depression take a heavy toll on women's mental health. The purpose of this study is to assess mental health among a sample of Mumbai slum-dwelling women with a history of recent childbirth, stillbirth, or infant death, who are at risk for perinatal grief, postnatal depression, or mental health sequelae. METHODS: We conducted a mixed method, cross-sectional study. A focus group discussion informed the development of a comprehensive survey using mainly internationally validated scales. After rigorous forward and back-translation, surveys were administered as face-to-face structured interviews due to low literacy and research naiveté among our respondents. Interviews were conducted by culturally, linguistically, gender-matched, trained research assistants. RESULTS: Of our reproductive age (N = 260) participants, 105 had experienced stillbirth, 69 had a history of infant death, and 25 had experienced both types of loss. Nearly half of the sample met criteria for postnatal depression, and 20% of these women also met criteria for perinatal grief. Anxiety and depression varied by subgroup, and was highest among women desiring an intervention. CONCLUSIONS: Understanding factors contributing to women's suffering related to reproductive challenges in this pronatalist context is critically important for women's wellbeing.


Asunto(s)
Depresión Posparto/epidemiología , Pesar , Muerte del Lactante , Madres/psicología , Mortinato/psicología , Adolescente , Adulto , Estudios Transversales , Depresión Posparto/diagnóstico , Depresión Posparto/prevención & control , Depresión Posparto/psicología , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , India/epidemiología , Lactante , Recién Nacido , Salud Mental/estadística & datos numéricos , Servicios de Salud Mental/organización & administración , Pobreza , Embarazo , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Investigación Cualitativa , Normas Sociales , Mortinato/epidemiología , Adulto Joven
3.
Phys Rev Lett ; 124(10): 101303, 2020 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-32216421

RESUMEN

This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81-3.31 µeV. This search utilizes the combination of a low-noise Josephson parametric amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics.

4.
Ann Oncol ; 30(Suppl_8): viii16-viii22, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31738428

RESUMEN

Due to the efficacy of tropomyosin receptor kinase (TRK) inhibitor therapy and the recent Food and Drug Administration approval of larotrectinib, it is now clinically important to accurately and efficiently identify patients with neurotrophic TRK (NTRK) fusion-driven cancer. These oncogenic fusions occur when the kinase domain of NTRK1, NTRK2 or NTRK3 fuse with any of a number of N-terminal partners. NTRK fusions are characteristic of a few rare types of cancer, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma, but they are also infrequently seen in some common cancers, such as melanoma, glioma and carcinomas of the thyroid, lung and colon. There are multiple methods for identifying NTRK fusions, including pan-TRK immunohistochemistry, fluorescence in situ hybridisation and sequencing methods, and the advantages and drawbacks of each are reviewed here. While testing algorithms will obviously depend on availability of various testing modalities and economic considerations for each individual laboratory, we propose triaging specimens based on histology and other molecular findings to most efficiently identify tumours harbouring these treatable oncogenic fusions.


Asunto(s)
Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas Receptoras/genética , Fusión Génica , Humanos , Glicoproteínas de Membrana/genética , Neoplasias/enzimología , Receptor trkA/genética , Receptor trkB/genética , Receptor trkC/genética
5.
Ann Oncol ; 30 Suppl 8: viii16-viii22, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-32223934

RESUMEN

Due to the efficacy of tropomyosin receptor kinase (TRK) inhibitor therapy and the recent Food and Drug Administration approval of larotrectinib, it is now clinically important to accurately and efficiently identify patients with neurotrophic TRK (NTRK) fusion-driven cancer. These oncogenic fusions occur when the kinase domain of NTRK1, NTRK2 or NTRK3 fuse with any of a number of N-terminal partners. NTRK fusions are characteristic of a few rare types of cancer, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma, but they are also infrequently seen in some common cancers, such as melanoma, glioma and carcinomas of the thyroid, lung and colon. There are multiple methods for identifying NTRK fusions, including pan-TRK immunohistochemistry, fluorescence in situ hybridisation and sequencing methods, and the advantages and drawbacks of each are reviewed here. While testing algorithms will obviously depend on availability of various testing modalities and economic considerations for each individual laboratory, we propose triaging specimens based on histology and other molecular findings to most efficiently identify tumours harbouring these treatable oncogenic fusions.


Asunto(s)
Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Neoplasias/diagnóstico , Receptor trkB/genética , Receptor trkB/metabolismo , Receptor trkC/genética , Receptor trkC/metabolismo
6.
Value Health ; 22(4): 408-415, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30975391

RESUMEN

OBJECTIVE: The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH. STUDY DESIGN: Trial-based cost-utility modeling analysis. METHODS: We performed an economic evaluation from a payer perspective using a Markov model with six health states: invasive disease-free survival, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, and death. We parameterized the model using data from both arms in APHINITY extrapolated to a patient's lifetime horizon. Estimates of health state utilities were based on EQ-5D trial data and the literature, and costs were estimated from government sources and the published literature. The primary outcomes of the model were life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed via univariate and probabilistic sensitivity analyses. RESULTS: For the intention-to-treat population, the model projected improved outcomes (by 0.50 LYs and 0.45 QALYs) and increased costs (by $74 420) for ICERs of $147 774/LY gained and $167 185/QALY gained for PHT vs. HT patients. In the node-positive patient population, the model projected improved outcomes (by 0.86 LYs and 0.76 QALYs) and increased costs (by $66 647) for ICERs of $77 684/LY gained and $87 929/QALY gained. For the hormone-receptor-negative patient population, the model projected health gains, increased costs, and ICERs of $147 022/LY gained and $166 518/QALY gained. The results were sensitive to changes in the model time horizon. CONCLUSION: The addition of pertuzumab to the available regimens for HER2+ early breast cancer is likely to be cost-effective for patients in the U.S. at high risk of recurrence.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/economía , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/economía , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/economía , Costos de los Medicamentos , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/administración & dosificación , Trastuzumab/economía , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante/economía , Ahorro de Costo , Análisis Costo-Beneficio , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Cadenas de Markov , Persona de Mediana Edad , Modelos Económicos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2/metabolismo , Factores de Tiempo , Trastuzumab/efectos adversos , Resultado del Tratamiento
7.
Value Health ; 22(2): 161-167, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30711060

RESUMEN

OBJECTIVE: The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration-approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC). STUDY DESIGN: A 2-state Markov model, alive and dead, with a lifetime horizon. METHODS: Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs. RESULTS: VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective. CONCLUSIONS: At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered.


Asunto(s)
Alelos , Análisis Costo-Beneficio , Terapia Genética/economía , Enfermedades de la Retina/economía , Enfermedades de la Retina/terapia , cis-trans-Isomerasas/economía , Adolescente , Adulto , Anciano , Análisis Costo-Beneficio/métodos , Femenino , Terapia Genética/métodos , Humanos , Masculino , Cadenas de Markov , Persona de Mediana Edad , Enfermedades de la Retina/genética , Trastornos de la Visión/economía , Trastornos de la Visión/genética , Trastornos de la Visión/terapia , Adulto Joven , cis-trans-Isomerasas/administración & dosificación , cis-trans-Isomerasas/genética
8.
Attach Hum Dev ; 21(4): 389-417, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30246604

RESUMEN

This exploratory study describes the development of a classification system for dogs' attachment security to caregivers that adheres closely to Ainsworth's seminal methodology. Fifty-nine adult dogs and caregivers participated in a mildly threatening laboratory encounter with a stranger (TS) and the Strange Situation (SSP). Dog and attachment experts adapted Ainsworth's classification system  for the behavioral repertoire of the dog. Four potentially comparable patterns of attachment were identified. The proportions of secure and insecure classifications (61% and 39%) were similar to those found in human toddlers. Caregivers' sensitivity to their dogs during the TS procedure significantly differentiated dogs with secure vs. insecure classifications Lower scores on the Active/excited personality scale on the Monash Canine Personality Questionnaire-Revised (MCPQ-R) also were related to secure classification. This system now makes it possible to compare directly the effects of human and dog attachment patterns on the health and emotional well-being of humans and dogs.


Asunto(s)
Conducta Animal , Vínculo Humano-Animal , Apego a Objetos , Adulto , Animales , Conducta Animal/fisiología , Perros , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
10.
Intern Med J ; 48(6): 624-636, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29582550

RESUMEN

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.


Asunto(s)
Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/terapia , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/terapia , Proteína ADAMTS13/genética , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Australia , Niño , Consenso , Síndrome Hemolítico-Urémico/genética , Humanos , Nueva Zelanda
11.
Nephrology (Carlton) ; 23(6): 507-517, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29419916

RESUMEN

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Intercambio Plasmático/normas , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/terapia , Proteína ADAMTS13/sangre , Proteína ADAMTS13/inmunología , Australia , Autoanticuerpos/sangre , Biomarcadores/sangre , Factor H de Complemento/inmunología , Consenso , Síndrome Hemolítico-Urémico/sangre , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/terapia , Humanos , Factores Inmunológicos/uso terapéutico , Nueva Zelanda , Valor Predictivo de las Pruebas , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/terapia , Factores de Riesgo , Rituximab/uso terapéutico , Escherichia coli Shiga-Toxigénica/aislamiento & purificación , Esteroides/uso terapéutico , Microangiopatías Trombóticas/sangre , Resultado del Tratamiento
12.
Reprod Health ; 15(1): 216, 2018 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-30577872

RESUMEN

BACKGROUND: Several cost-effective programs are being implemented around the world that use mobile technology to improve Sexual and Reproductive Health (SRH) uptake and awareness among youth. Mobile phone applications are a viable and effective means of increasing access to SRH services and tools in low and middle-income countries. This paper presents a protocol for a pilot study of a novel program, a mobile phone-based sexual and reproductive health services awareness and delivery application with the objective of increasing the demand for SRH services amongst the youth in Uganda. METHODS: The study employs rigorous evaluation methods to ascertain the impact of the mobile application. We propose a randomized control trial study to determine the causal effect of the mobile phone app in creating awareness and increasing uptake of sexual and reproductive health services in Uganda. The main outcome of the impact evaluation is the percentage change in the SRH services and tools uptake, SRH knowledge and sexual behavior. We will also conduct a model-based incremental cost-effectiveness analysis (CEA) and budget impact analysis (BIA). The main outcomes of the economic evaluation will be the average cost per app user, cost per app service and tool provided. We will also test the in-app advertising model as a way to generate revenue to sustain the program subsidies and related costs. DISCUSSION: The study seeks to establish the proof of concept of using a mobile application to increase create awareness and increase uptake of SRH tools and services among youth in Uganda. The study results will lead to the development of a demand-driven, culturally-relevant, and easy-to-use mobile app to enhance the uptake of SRH services among the youth in Uganda and globally. TRIAL REGISTRATION: MUREC1/7 No. 07/05-18 . Registered 29th June 2018.


Asunto(s)
Teléfono Celular/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud/métodos , Aplicaciones Móviles/estadística & datos numéricos , Servicios de Salud Reproductiva/estadística & datos numéricos , Salud Reproductiva/educación , Conducta Sexual/psicología , Adolescente , Adulto , Femenino , Humanos , Masculino , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Uganda , Adulto Joven
13.
Parasitology ; 144(11): 1468-1475, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28641605

RESUMEN

Parasites can evolve phenotypically plastic strategies for transmission such that a single genotype can give rise to a range of phenotypes depending on the environmental condition. State-dependent plasticity in particular can arise from individual differences in the parasite's internal state or the condition of the host. Facultative parasites serve as ideal model systems for investigating state-dependent plasticity because individuals can exhibit two life history strategies (free-living or parasitic) depending on the environment. Here, we experimentally show that the ectoparasitic mite Macrocheles subbadius is more likely to parasitize a fruit fly host if the female mite is mated; furthermore, the propensity to infect increased with the level of starvation experienced by the mite. Host condition also played an important role; hosts infected with moderate mite loads were more likely to gain additional infections in pairwise choice tests than uninfected flies. We also found that mites preferentially infected flies subjected to mechanical injury over uninjured flies. These results suggest that a facultative parasite's propensity to infect a host (i.e. switch from a free-living strategy) depends on both the parasite's internal state and host condition. Parasites often live in highly variable and changing environments, an infection strategy that is plastic is likely to be adaptive.


Asunto(s)
Drosophila/parasitología , Interacciones Huésped-Parásitos , Ácaros/fisiología , Animales , Evolución Biológica , Drosophila/fisiología , Ambiente , Femenino , Genotipo , Especificidad del Huésped , Fenotipo , Simbiosis
14.
Inhal Toxicol ; 29(11): 506-515, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-29224407

RESUMEN

Aerosol aerodynamic particle size is known to affect deposition patterns of inhaled aerosol particles, as well as the virulence of inhaled bioaerosol particles. While a significant amount of work has been performed to describe the deposition of aerosol particles in the human respiratory tract, only a limited amount of work has been performed to describe the deposition of aerosol particles in the respiratory tract of nonhuman primates, an animal model commonly utilized in pharmacological and toxicological studies, especially in the biodefense field. In this study, anesthetized rhesus macaques inhaled radiolabeled aerosols with MMADs of 1.7, 3.6, 7.4 and 11.8 µm to characterize regional deposition patterns. The results demonstrate that the regional deposition pattern shifts as particle size increases, with greater deposition in more proximal regions of the respiratory tract and decreased deposition in the pulmonary region. The results of this study extend the findings of previous studies which demonstrated a similar shift in the deposition pattern as a function of particle size by providing greater resolution of deposition patterns. These data on regional deposition patterns provide a starting point to begin to explore potential mechanisms responsible for the differences in virulence of infectious bioaerosols as a function of particle size and deposition pattern reported in previous studies. Additionally, the data are useful to assess the performance of various deposition models that have been published in the literature.


Asunto(s)
Fluorodesoxiglucosa F18/administración & dosificación , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/administración & dosificación , Aerosoles , Animales , Femenino , Interpretación de Imagen Asistida por Computador , Exposición por Inhalación , Pulmón/virología , Macaca mulatta , Masculino , Tamaño de la Partícula , Valor Predictivo de las Pruebas , Virión
15.
BMC Health Serv Res ; 17(1): 638, 2017 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-28893243

RESUMEN

BACKGROUND: Poor access to essential medicines is common in many low- and middle-income countries, partly due to an insufficient and inadequately trained workforce to manage the medicines supply chain. We conducted a prospective impact evaluation of the training and deployment of pharmacy assistants (PAs) to rural health centers in Malawi. METHODS: A quasi-experimental design was used to compare access to medicines in two districts where newly trained PAs were deployed to health centers (intervention) and two districts with no trained PAs at health centers (comparison). A baseline household survey and two annual post-intervention household surveys were conducted. We studied children under five years with a history of fever, cough and difficulty in breathing, and diarrhea in the previous two weeks. We collected data on access to antimalarials, antibiotics and oral rehydration salts (ORS) during the childrens' symptomatic periods. We used difference-in-differences regression models to estimate the impact of PA training and deployment on access to medicines. RESULTS: We included 3974 children across the three rounds of annual surveys: 1840 (46%) in the districts with PAs deployed at health centers and 2096 (53%) in districts with no PAs deployed at health centers. Approximately 80% of children had a fever, nearly 30% had a cough, and 43% had diarrhea in the previous two weeks. In the first year of the program, the presence of a PA led to a significant 74% increase in the odds of access to any antimalarial, and a significant 49% increase in the odds of access to artemisinin combination therapies. This effect was restricted to the first year post-intervention. There was no effect of presence of a PA on access to antibiotics or ORS. CONCLUSION: The training and deployment of pharmacy assistants to rural health centers in Malawi increased access to antimalarial medications over the first year, but the effect was attenuated over the second year. Pharmacy assistants training and deployment demonstrated no impact on access to antibiotics for pneumonia or oral rehydration salts for diarrhea.


Asunto(s)
Medicamentos Esenciales/provisión & distribución , Personal de Salud/educación , Accesibilidad a los Servicios de Salud , Servicios Farmacéuticos , Adulto , Preescolar , Análisis por Conglomerados , Femenino , Encuestas de Atención de la Salud , Humanos , Lactante , Malaui , Masculino , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Adulto Joven
16.
J Hum Nutr Diet ; 30(6): 709-713, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28799179

RESUMEN

BACKGROUND: Treatment of inflammatory bowel disease (IBD) involves a multidisciplinary approach comprising medical management and sometimes surgery. Although diet is central to IBD management, the optimal diet for patients with IBD is uncertain. A UK collaborative partnership within the James Lind Alliance was set up between patients, clinicians and other stakeholders to develop research priorities in IBD. The aim of this short report is to provide a comprehensive summary of the research priority findings relating to diet in the treatment of IBD. METHODS: The James Lind Alliance Priority Setting Partnership process was used to develop research priorities in IBD. In brief, patients, clinicians and other stakeholders were invited to provide up to five treatment uncertainties in IBD. These uncertainties were collated, revised and ranked, leading to a final top 10 research questions in IBD. RESULTS: A total of 1671 uncertainties from 531 participants were collected and refined to exclude duplicates leaving 1253 uncertainties. Of these, 348 were categorised as diet-related and grouped according to topic. There were 206 uncertainties related to how diet can be used to treat IBD or alleviate symptoms. Seventy-two percent of diet-related questions came from patients. One broadly diet-related and two diet-specific treatment uncertainties were included in the top 10 research priorities for IBD. CONCLUSIONS: Dietary treatment options in the management of IBD are important research priorities. Almost three-quarters of diet related questions came from patients, who were particularly interested in how diet can impact disease activity and symptom control.


Asunto(s)
Dieta , Enfermedades Inflamatorias del Intestino/dietoterapia , Suplementos Dietéticos , Manejo de la Enfermedad , Nutrición Enteral , Tracto Gastrointestinal/microbiología , Humanos , Micronutrientes/administración & dosificación , Probióticos/administración & dosificación , Encuestas y Cuestionarios , Incertidumbre
17.
Reprod Health ; 14(1): 140, 2017 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-29078815

RESUMEN

BACKGROUND: The use of contraception is one of the most cost-effective public health interventions and has the potential to prevent about 30% of maternal and 10% of child deaths in developing countries. Voucher-based initiatives for family planning are an effective and viable means of increasing contraceptive use. In this paper, we present a protocol for a pilot study of a novel incentive, a family planning benefits card (FPBC) program to increase uptake of family planning services among urban poor youth in Uganda while leveraging private sector funding. METHODS: The study employs both impact and health economic evaluation methods to assess the effect of the FPBC program. We propose a quasi-experimental study design with two separate pre- and post-samples to measure program effectiveness. The main outcome of the impact evaluation is the percentage change in the prevalence of modern contraceptive use and unmet need for contraception. We will also conduct model-based incremental cost-effectiveness and budget impact analyses. The main outcomes of the economic evaluation are the cost per enrolled youth and cost per pregnancy averted, and cost per disability-adjusted life-year (DALY) averted. We will also pilot a corporate social responsibility model of sponsorship for the FPBC program in partnership with local corporations. Budget impact analysis will examine the potential affordability of scaling up the FPBC program and the fiscal implications of this scale up to the corporate social responsibility (CSR) budgets of partner corporations, the government, and the individual taxpayer. DISCUSSION: In this study, we propose an impact and economic evaluation to establish the proof concept of using a FPBC program to increase uptake of family planning services among urban poor youth in Uganda. The results of this study will present stakeholders in Uganda and internationally with a potentially viable option for corporate-sponsored access to family planning in urban poor communities. TRIAL REGISTRATION: MUREC1/7 No. 10/05-17. Registered 19th July 2017.


Asunto(s)
Anticoncepción/economía , Atención a la Salud/economía , Servicios de Planificación Familiar/economía , Accesibilidad a los Servicios de Salud/economía , Educación Sexual/economía , Adolescente , Adulto , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Proyectos Piloto , Uganda , Población Urbana , Adulto Joven
18.
Exp Brain Res ; 233(7): 1993-2000, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25912606

RESUMEN

In order to determine the influence of perceptual input upon oculomotor responses, we examined rapid saccadic eye movements made by healthy human observers to a virtual target defined by the extrapolated intersection of a pointer with a distant landing line. While corresponding perceptual judgments showed no evidence of systematic bias, eye movements showed a strong bias, in the direction of assimilation of the saccade trajectory to the shortest path between the end of the pointer and the landing line. Adding an abutting vertical inducing line to make an angle of 45 deg with the pointer led to a larger bias in the same direction as the classical Poggendorff illusion. This additional Poggendorff effect was similar in direction and magnitude for the eye movements and the perceptual responses. Latency and dynamics of the eye movements were closely similar to those recorded for a control task in which observers made a saccade from the start fixation to an explicit target on the landing line. Further experiments with inducing lines presented briefly at various times during the saccade latency period showed that the magnitude of the saccade bias was affected by inducer presentation during the saccade planning process, but not during the saccade itself. We conclude that the neural mechanisms for extrapolation can feed into the control of eye movements without obvious penalties in timing and accuracy and that this information can instantaneously modify motor response throughout the planning phase, suggesting close association between perceptual and motor mechanisms in the process of visuo-spatial extrapolation.


Asunto(s)
Sesgo , Ilusiones/fisiología , Movimientos Sacádicos/fisiología , Análisis de Varianza , Femenino , Humanos , Masculino , Estimulación Luminosa , Tiempo de Reacción , Interfaz Usuario-Computador
19.
Nephrol Dial Transplant ; 29(3): 698-705, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24009292

RESUMEN

BACKGROUND: Prednisolone is a major risk factor for hyperglycaemia and new-onset diabetes after transplantation. Uncontrolled observational data suggest that divided dosing may reduce requirements for hypoglycaemic agents. This study aims to compare the glycaemic effects of divided twice daily (BD) and once daily (QD) prednisolone. METHODS: Twenty-two kidney transplant recipients without diabetes were randomized to BD or QD prednisolone. Three weeks post-transplant, a continuous glucose monitor (iPro2(®) Medtronic) was applied for 5 days with subjects continuing their initial prednisolone regimen (Days 1-2) before crossover to the alternative regimen. Mean glucose, peak glucose, nadir glucose, exposure to hyperglycaemia (glucose ≥7.8 mmol/L) and glycaemic variability were assessed. RESULTS: The mean ± standard deviation (SD) age of subjects was 50 ± 10 years and 77% were male. Median (interquartile range) daily prednisolone dose was 25 (20, 25) mg. BD prednisolone was associated with decreased mean glucose (mean 7.9 ± 1.7 versus 8.1 ± 2.3 mmol/L, P < 0.001), peak glucose [median 10.4 (9.5, 11.4) versus 11.4 (10.3, 13.4) mmol/L, P< 0.001] and exposure to hyperglycaemia [median 25.5 (14.6, 30.3) versus 40.4 (33.2, 51.2) mmol/L/h, P = 0.003]. Median glucose peaked between 14:55-15.05 h with BD and 15:25-15:30 h with QD. Median glycaemic variability scores were decreased with BD: SD (1.1 versus 1.9, P < 0.001), mean amplitude of glycaemic excursion (1.5 versus 2.2, P = 0.001), continuous overlapping net glycaemic action-1 (CONGA-1; 1.0 versus 1.2, P = 0.039), CONGA-2 (1.2 versus 1.4, P = 0.008) and J-index (25 versus 31, P = 0.003). CONCLUSIONS: Split prednisolone dosing reduces glycaemic variability and hyperglycaemia early post-kidney transplant.


Asunto(s)
Hiperglucemia/inducido químicamente , Inmunosupresores/efectos adversos , Prednisolona/efectos adversos , Adulto , Glucemia , Estudios Cruzados , Esquema de Medicación , Femenino , Humanos , Hiperglucemia/sangre , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Factores de Riesgo
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