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1.
Angew Chem Int Ed Engl ; 62(31): e202305810, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37276357

RESUMEN

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a "base-free" approach to ß-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac)3 was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee).

2.
PLoS One ; 17(10): e0274304, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36206230

RESUMEN

BACKGROUND: Use of a standardized verbal autopsy (VA) questionnaire, such as the World Health Organization (WHO) instrument, can improve the consistency and reliability of the data it collects. Systematically revising a questionnaire, however, requires evidence about the performance of its questions. The purpose of this investigation was to use a mixed methods approach to evaluate the performance of questions related to 14 previously reported issues in the 2016 version of the WHO questionnaire, where there were concerns of potential confusion, redundancy, or inability of the respondent to answer the question. The results from this mixed methods analysis are discussed across common themes that may have contributed to the underperformance of questions and have been compiled to inform decisions around the revision of the current VA instrument. METHODS: Quantitative analysis of 19,150 VAs for neonates, children, and adults from five project teams implementing VAs predominately in Sub-Saharan Africa included frequency distributions and cross-tabulations to evaluate response patterns among related questions. The association of respondent characteristics and response patterns was evaluated using prevalence ratios. Qualitative analysis included results from cognitive interviewing, an approach that provides a detailed understanding of the meanings and processes that respondents use to answer interview questions. Cognitive interviews were conducted among 149 participants in Morocco and Zambia. Findings from the qualitative and quantitative analyses were triangulated to identify common themes. RESULTS: Four broad themes contributing to the underperformance or redundancy within the instrument were identified: question sequence, overlap within the question series, questions outside the frame of reference of the respondent, and questions needing clarification. The series of questions associated with one of the 14 identified issues (the series of questions on injuries) related to question sequence; seven (tobacco use, sores, breast swelling, abdominal problem, vomiting, vaccination, and baby size) demonstrated similar response patterns among questions within each series capturing overlapping information. Respondent characteristics, including relationship to the deceased and whether or not the respondent lived with the deceased, were associated with differing frequencies of non-substantive responses in three question series (female health related issues, tobacco use, and baby size). An inconsistent understanding of related constructs was observed between questions related to sores/ulcers, birth weight/baby size, and diagnosis of dementia/presence of mental confusion. An incorrect association of the intended construct with that which was interpreted by the respondent was observed in the medical diagnosis question series. CONCLUSIONS: In this mixed methods analysis, we identified series of questions which could be shortened through elimination of redundancy, series of questions requiring clarification due to unclear constructs, and the impact of respondent characteristics on the quality of responses. These changes can lead to a better understanding of the question constructs by the respondents, increase the acceptance of the tool, and improve the overall accuracy of the VA instrument.


Asunto(s)
Autopsia , Adulto , Autopsia/métodos , Niño , Femenino , Humanos , Recién Nacido , Marruecos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Organización Mundial de la Salud
3.
Int J Epidemiol ; 51(5): 1457-1468, 2022 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-35441222

RESUMEN

BACKGROUND: Household contacts who provide care to an Ebola virus disease (EVD) case have a 3-fold higher risk of EVD compared with contacts who do not provide care. METHODS: We enrolled persons with confirmed EVD from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index cases and contacts were interviewed, and contacts were followed for 21 days to identify secondary cases. Epidemiological data were analysed to describe household care and to identify risk factors for developing EVD. RESULTS: Of 838 contacts in 147 households, 156 (17%) self-reported providing care to the index case; 56 households had no care provider, 52 a single care provider and 39 multiple care providers. The median care provider age was 29 years, 68% were female and 32% were the index case's spouse. Care providers were more likely to report physical contact, contact with body fluids or sharing clothing, bed linens or utensils with an index case, compared with non-care providers (P <0.01). EVD risk among non-care providers was greater when the number of care providers in the household increased (odds ratio: 1.61; 95% confidence interval: 1.1, 2.4). In multivariable analysis, factors associated with care provider EVD risk included no piped water access and absence of index case fever, and protective factors included age <20 years and avoiding the index case. CONCLUSIONS: Limiting the number of care providers in a household could reduce the risk of EVD transmission to both care providers and non-care providers. Strategies to protect care providers from EVD exposure are needed.


Asunto(s)
Fiebre Hemorrágica Ebola , Adulto , Brotes de Enfermedades , Composición Familiar , Femenino , Fiebre , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Masculino , Factores de Riesgo , Sierra Leona/epidemiología , Adulto Joven
4.
Sex Abuse ; 34(1): 52-77, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33586525

RESUMEN

This study explores future mental health providers' assumptions about minor-attracted people, using data from a survey of 200 students preparing for entry into social service professions at a public university in the state of Utah. Survey results show that more than half of the students believe clients who identify themselves as pedophiles must be automatically reported to the police, which has implications for providers' understandings about the term "pedophile," as well as their knowledge of guidelines for when clinicians may break client confidentiality. This belief was not significantly affected by taking ethics courses, nor courses that discussed mandated reporting guidelines. Despite this finding, 91% of students did not believe that they would need to report a client who had attractions to children, but who had never committed a sexual offense against a child. The majority of students indicated a willingness to work with minor-attracted clients, and commonly indicated in comments that they wanted more information about MAPs and when to break client confidentiality in their programs of study. Study results indicate a need for education among social service students about these issues.


Asunto(s)
Actitud , Universidades , Niño , Conocimientos, Actitudes y Práctica en Salud , Humanos , Servicio Social , Estudiantes , Encuestas y Cuestionarios
5.
Eur J Ophthalmol ; 32(3): NP46-NP49, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-33525898

RESUMEN

Thyroid eye disease is an auto-immune mediated orbitopathy which can cause dysthyroid compressive optic neuropathy. Traditional management of active thyroid eye disease includes temporizing high-dose steroids, orbital radiation and surgical decompression, which each possess significant limitations and/or side effects. Teprotumumab is an IGF-IR inhibitor recently FDA-approved for active thyroid eye disease. The authors report reversal of bilateral dysthyroid compressive optic neuropathy managed medically utilizing teprotumumab.


Asunto(s)
Oftalmopatía de Graves , Enfermedades del Nervio Óptico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Descompresión Quirúrgica , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/cirugía , Humanos , Nervio Óptico , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/etiología
6.
MMWR Morb Mortal Wkly Rep ; 70(49): 1706-1711, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34882655

RESUMEN

Immediately following the March 13, 2020 declaration of COVID-19 as a national emergency (1), the U.S. government began implementing national testing programs for epidemiologic surveillance, monitoring of frontline workers and populations at higher risk for acquiring COVID-19, and identifying and allocating limited testing resources. Effective testing supports identification of COVID-19 cases; facilitates isolation, quarantine, and timely treatment measures that limit the spread of SARS-CoV-2 (the virus that causes COVID-19); and guides public health officials about the incidence of COVID-19 in a community. A White House Joint Task Force, co-led by the Department of Health and Human Services (HHS) and the Federal Emergency Management Agency (FEMA), created the Community-Based Testing Sites (CBTS) program working with state and local partners (2). This report describes the timeline, services delivered, and scope of the CBTS program. During March 19, 2020-April 11, 2021, the CBTS program conducted 11,661,923 SARS-CoV-2 tests at 8,319 locations across the United States and its territories, including 402,223 (3.5%) administered through Drive-Through Testing, 10,129,142 (86.9%) through Pharmacies+ Testing, and 1,130,558 (9.7%) through Surge Testing programs. Tests administered through the CBTS program yielded 1,176,959 (10.1%) positive results for SARS-CoV-2. Among tested persons with available race data,* positive test results were highest among American Indian or Alaska Native (14.1%) and Black persons (10.4%) and lowest among White persons (9.9%), Asian persons (7.3%), and Native Hawaiian or Other Pacific Islanders (6.4%). Among persons with reported ethnicity, 25.3% were Hispanic, 15.9% of whom received a positive test result. Overall, 82.0% of test results were returned within 2 days, but the percentage of test results returned within 2 days was as low as 40.7% in July 2020 and 59.3% in December 2020 during peak testing periods. Strong partnerships enabled a rapid coordinated response to establish the federally supported CBTS program to improve access to no-charge diagnostic testing, including for frontline workers, symptomatic persons and close contacts, and persons living in high-prevalence areas. In April 2021, the CBTS Pharmacies+ Testing and Surge Testing programs were expanded into the Increasing Community Access to Testing (ICATT) program. As of November 12, 2021, the CBTS and ICATT programs conducted approximately 26.6 million tests with approximately 10,000 active testing sites. Although the CBTS program represented a relatively small portion of overall U.S. SARS-CoV-2 testing, with its successful partnerships and adaptability, the CBTS program serves as a model to guide current community-based screening, surveillance, and disease control programs, and responses to future public health emergencies.


Asunto(s)
Prueba de COVID-19/estadística & datos numéricos , COVID-19/diagnóstico , Servicios de Salud Comunitaria/organización & administración , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Conducta Cooperativa , Femenino , Accesibilidad a los Servicios de Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Relaciones Interinstitucionales , Masculino , Área sin Atención Médica , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Estados Unidos/epidemiología , Adulto Joven
7.
Glob Health Action ; 14(sup1): 1982486, 2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-35377290

RESUMEN

Over the past 70 years, significant advances have been made in determining the causes of death in populations not served by official medical certification of cause at the time of death using a technique known as Verbal Autopsy (VA). VA involves an interview of the family or caregivers of the deceased after a suitable bereavement interval about the circumstances, signs and symptoms of the deceased in the period leading to death. The VA interview data are then interpreted by physicians or, more recently, computer algorithms, to assign a probable cause of death. VA was originally developed and applied in field research settings. This paper traces the evolution of VA methods with special emphasis on the World Health Organization's (WHO)'s efforts to standardize VA instruments and methods for expanded use in routine health information and vital statistics systems in low- and middle-income countries (LMICs). These advances in VA methods are culminating this year with the release of the 2022 WHO Standard Verbal Autopsy (VA) Toolkit. This paper highlights the many contributions the late Professor Peter Byass made to the current VA standards and methods, most notably, the development of InterVA, the most commonly used automated computer algorithm for interpreting data collected in the WHO standard instruments, and the capacity building in low- and middle-income countries (LMICs) that he promoted. This paper also provides an overview of the methods used to improve the current WHO VA standards, a catalogue of the changes and improvements in the instruments, and a mapping of current applications of the WHO VA standard approach in LMICs. It also provides access to tools and guidance needed for VA implementation in Civil Registration and Vital Statistics Systems at scale.


Asunto(s)
Estadísticas Vitales , Autopsia/métodos , Causas de Muerte , Certificación , Humanos , Masculino , Pobreza
9.
Clin Cancer Res ; 26(16): 4268-4279, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32398324

RESUMEN

PURPOSE: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial of PARPi olaparib and anti-PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis. PATIENTS AND METHODS: In a single-center, proof-of-concept phase II study, we enrolled women aged ≥18 with recurrent ovarian cancer. All patients were immune checkpoint inhibitor-naïve and had measurable disease per RECISTv1.1, ECOG performance status 0-2, and adequate organ and marrow function. Patients received olaparib 300 mg twice daily and durvalumab 1,500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint was overall response rate (ORR). Secondary objectives were safety and progression-free survival (PFS). Translational objectives included biomarker evaluation for relationships with clinical response and immunomodulatory effects by treatment. RESULTS: Thirty-five patients with ovarian cancer [median, four prior therapies (IQR, 2-5.5), predominantly platinum-resistant (86%), BRCA wild-type (77%)] received at least one full cycle of treatment. ORR was 14% [5/35; 95% confidence interval (CI), 4.8%-30.3%]. Disease control rate (PR+SD) was 71% (25/35; 95% CI, 53.7%-85.4%). Treatment enhanced IFNγ and CXCL9/CXCL10 expression, systemic IFNγ/TNFα production, and tumor-infiltrating lymphocytes, indicating an immunostimulatory environment. Increased IFNγ production was associated with improved PFS [HR, 0.37 (95% CI, 0.16-0.87), P = 0.023], while elevated VEGFR3 levels were associated with worse PFS (HR, 3.22 (95% CI, 1.23-8.40), P = 0.017]. CONCLUSIONS: The PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Our correlative study results suggest immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antígeno B7-H1/genética , Neoplasias Ováricas/tratamiento farmacológico , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Poli(ADP-Ribosa) Polimerasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Quimiocina CXCL10/genética , Quimiocina CXCL9/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Interferón gamma/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Supervivencia sin Progresión , Factor A de Crecimiento Endotelial Vascular/genética
11.
PLoS Med ; 16(9): e1002929, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31560684

RESUMEN

BACKGROUND: Civil registration and vital statistics (CRVS) systems play a key role in upholding human rights and generating data for health and good governance. They also can help monitor progress in achieving the United Nations Sustainable Development Goals. Although many countries have made substantial progress in strengthening their CRVS systems, most low- and middle-income countries still have underdeveloped systems. The objective of this systematic review is to identify national policies that can help countries strengthen their systems. METHODS AND FINDINGS: The ABI/INFORM, Embase, JSTOR, PubMed, and WHO Index Medicus databases were systematically searched for policies to improve birth and/or death registration on 24 January 2017. Global stakeholders were also contacted for relevant grey literature. For the purposes of this review, policies were categorised as supply, demand, incentive, penalty, or combination (i.e., at least two of the preceding policy approaches). Quantitative results on changes in vital event registration rates were presented for individual comparative articles. Qualitative systematic review methodology, including meta-ethnography, was used for qualitative syntheses on operational considerations encompassing acceptability to recipients and staff, human resource requirements, information technology or infrastructure requirements, costs to the health system, unintended effects, facilitators, and barriers. This study is registered with PROSPERO, number CRD42018085768. Thirty-five articles documenting experience in implementing policies to improve birth and/or death registration were identified. Although 25 countries representing all global regions (Africa, the Americas, Southeast Asia, the Western Pacific, Europe, and the Eastern Mediterranean) were reflected, there were limited countries from the Eastern Mediterranean and Europe regions. Twenty-four articles reported policy effects on birth and/or death registration. Twenty-one of the 24 articles found that the change in registration rate after the policy was positive, with two supply and one penalty articles being the exceptions. The qualitative syntheses identified 15 operational considerations across all policy categories. Human and financial resource requirements were not quantified. The primary limitation of this systematic review was the threat of publication bias wherein many countries may not have documented their experience; this threat is most concerning for policies that had neutral or negative effects. CONCLUSIONS: Our systematic review suggests that combination policy approaches, consisting of at least a supply and demand component, were consistently associated with improved registration rates in different geographical contexts. Operational considerations should be interpreted based on health system, governance, and sociocultural context. More evaluations and research are needed from the Eastern Mediterranean and Europe regions. Further research and evaluation are also needed to estimate the human and financial resource requirements required for different policies.


Asunto(s)
Exactitud de los Datos , Recolección de Datos/métodos , Derechos Humanos , Formulación de Políticas , Vigilancia de la Población/métodos , Salud Pública/métodos , Sistema de Registros , Estadísticas Vitales , Recolección de Datos/estadística & datos numéricos , Derechos Humanos/estadística & datos numéricos , Humanos , Salud Pública/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos
12.
J Immunother Cancer ; 7(1): 197, 2019 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-31345267

RESUMEN

BACKGROUND: Strategies to improve activity of immune checkpoint inhibitors are needed. We hypothesized enhanced DNA damage by olaparib, a PARP inhibitor, and reduced VEGF signaling by cediranib, a VEGFR1-3 inhibitor, would complement anti-tumor activity of durvalumab, a PD-L1 inhibitor, and the 3-drug combination would be tolerable. METHODS: This phase 1 study tested the 3-drug combination in a 3 + 3 dose escalation. Cediranib was taken intermittently (5 days on/2 days off) at 15 or 20 mg (dose levels 1 and 2, respectively) with durvalumab 1500 mg IV every 4 weeks, and olaparib tablets 300 mg twice daily. The primary end point was the recommended phase 2 dose (RP2D). Response rate, pharmacokinetic (PK), and correlative analyses were secondary endpoints. RESULTS: Nine patients (7 ovarian/1 endometrial/1 triple negative breast cancers, median 3 prior therapies [2-6]) were treated. Grade 3/4 adverse events include hypertension (1/9), anemia (1/9) and lymphopenia (3/9). No patients experienced dose limiting toxicities. The RP2D is cediranib, 20 mg (5 days on/2 days off) with full doses of durvalumab and olaparib. Four patients had partial responses (44%) and 3 had stable disease lasting ≥6 months, yielding a 67% clinical benefit rate. No significant effects on olaparib or cediranib PK parameters from the presence of durvalumab, or the co-administration of cediranib or olaparib were identified. Tumoral PD-L1 expression correlated with clinical benefit but cytokines and peripheral immune subsets did not. CONCLUSIONS: The RP2D is tolerable and has preliminary activity in recurrent women's cancers. A phase 2 expansion study is now enrolling for recurrent ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02484404. Registered June 29, 2015.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Neoplasias Endometriales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Quinazolinas/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Antígeno B7-H1/metabolismo , Esquema de Medicación , Neoplasias Endometriales/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Ováricas/metabolismo , Ftalazinas/farmacocinética , Piperazinas/farmacocinética , Quinazolinas/farmacocinética , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/metabolismo
13.
Glob Health Action ; 12(1): 1597452, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31179875

RESUMEN

Background: Efforts to improve national civil registration and vital statistics (CRVS) systems are focusing on transforming traditionally passive systems into active systems that have the ability to reach the household level. While community health agents remain at the core of many birth and death reporting efforts, previous literature has not explored elements for their successful integration into CRVS efforts. Objective: To inform future efforts to improve CRVS systems, we conducted a systematic review of literature to understand and describe the design features, resulting data quality, and factors impacting the performance of community health agents involved in tracking vital events. Methods: We reviewed 393 articles; reviewers extracted key information from 58 articles meeting the eligibility criteria: collection of birth and/or death information outside of a clinic environment by a community agent. Reviewers recorded information in an Excel database on various program aspects, and results were summarized into key themes and topic areas. Results: The majority of articles described work in rural areas of Africa or South-East Asia. Nearly all articles (86%) cited some form of household visitation by community health agents. Only one article described a process in which vital events tracking activities were linked to official vital events registers. Other factors commonly described included program costs, relationship of community agents to community, and use of mobile devices. About 1/3 of articles reported quantitative information on performance and quality of vital events data tracked; various methods were described for measuring completeness of reporting, which varied greatly across articles. Conclusions: The multitude of articles on this topic attests to the availability of community health agents to track vital events. Creating a programmatic norm of integrating with CRVS systems the vital events information collected from existing community health programs has the potential to provide governments with information essential for public health decision-making.


Asunto(s)
Certificado de Nacimiento , Causas de Muerte , Certificado de Defunción , Vigilancia de la Población/métodos , Salud Pública/estadística & datos numéricos , Estadísticas Vitales , Femenino , Humanos , Masculino
14.
J Immunother Cancer ; 6(1): 141, 2018 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-30514390

RESUMEN

BACKGROUND: Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC). Data from other trials suggest there may be improved activity in men with DNA damage repair (DDR) mutations treated with checkpoint inhibitors. This trial evaluated durvalumab and olaparib in patients with mCRPC with and without somatic or germline DDR mutations. METHODS: Eligible patients had received prior enzalutamide and/or abiraterone. Patients received durvalumab 1500 mg i.v. every 28 days and olaparib 300 mg tablets p.o. every 12 h until disease progression or unacceptable toxicity. All patients had biopsies of metastatic lesions with an evaluation for both germline and somatic mutations. RESULTS: Seventeen patients received durvalumab and olaparib. Nausea was the only nonhematologic grade 3 or 4 toxicity occurring in > 1 patient (2/17). No patients were taken off trial for toxicity. Median radiographic progression-free survival (rPFS) for all patients is 16.1 months (95% CI: 4.5-16.1 months) with a 12-month rPFS of 51.5% (95% CI: 25.7-72.3%). Activity is seen in patients with alterations in DDR genes, with a median rPFS of 16.1 months (95% CI: 7.8-18.1 months). Nine of 17 (53%) patients had a radiographic and/or PSA response. Patients with fewer peripheral myeloid-derived suppressor cells and with alterations in DDR genes were more likely to respond. Early changes in circulating tumor cell counts and in both innate and adaptive immune characteristics were associated with response. CONCLUSIONS: Durvalumab plus olaparib has acceptable toxicity, and the combination demonstrates efficacy, particularly in men with DDR abnormalities. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02484404 .


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Daño del ADN , Reparación del ADN , Mutación , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Humanos , Estimación de Kaplan-Meier , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Retratamiento , Resultado del Tratamiento
15.
J Infect Dis ; 218(5): 757-767, 2018 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-29659910

RESUMEN

Background: Knowing risk factors for household transmission of Ebola virus is important to guide preventive measures during Ebola outbreaks. Methods: We enrolled all confirmed persons with Ebola who were the first case in a household, December 2014-April 2015, in Freetown, Sierra Leone, and their household contacts. Cases and contacts were interviewed, contacts followed prospectively through the 21-day incubation period, and secondary cases confirmed by laboratory testing. Results: We enrolled 150 index Ebola cases and 838 contacts; 83 (9.9%) contacts developed Ebola during 21-day follow-up. In multivariable analysis, risk factors for transmission included index case death in the household, Ebola symptoms but no reported fever, age <20 years, more days with wet symptoms; and providing care to the index case (P < .01 for each). Protective factors included avoiding the index case after illness onset and a piped household drinking water source (P < .01 for each). Conclusions: To reduce Ebola transmission, communities should rapidly identify and follow-up all household contacts; isolate those with Ebola symptoms, including those without reported fever; and consider closer monitoring of contacts who provided care to cases. Households could consider efforts to minimize risk by designating one care provider for ill persons with all others avoiding the suspected case.


Asunto(s)
Transmisión de Enfermedad Infecciosa , Composición Familiar , Salud de la Familia , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/transmisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Sierra Leona/epidemiología , Adulto Joven
16.
PLoS Med ; 15(1): e1002486, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29320495

RESUMEN

BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable causes of death at the population level in places where systems for medical certification of cause of death are weak. VA methods suitable for use in routine settings, such as civil registration and vital statistics (CRVS) systems, have developed rapidly in the last decade. These developments have been part of a growing global momentum to strengthen CRVS systems in low-income countries. With this momentum have come pressure for continued research and development of VA methods and the need for a single standard VA instrument on which multiple automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016, partners harmonized a WHO VA standard instrument that fully incorporates the indicators necessary to run currently available automated diagnostic algorithms. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality. This VA instrument offers the opportunity to harmonize the automated diagnostic algorithms in the future. CONCLUSIONS: Despite all improvements in design and technology, VA is only recommended where medical certification of cause of death is not possible. The method can nevertheless provide sufficient information to guide public health priorities in communities in which physician certification of deaths is largely unavailable. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality.


Asunto(s)
Autopsia/métodos , Autopsia/normas , Estadísticas Vitales , Organización Mundial de la Salud , Causas de Muerte , Humanos
17.
Glob Health Action ; 10(1): 1272882, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28137194

RESUMEN

BACKGROUND: Reliable and representative cause of death (COD) statistics are essential to inform public health policy, respond to emerging health needs, and document progress towards Sustainable Development Goals. However, less than one-third of deaths worldwide are assigned a cause. Civil registration and vital statistics (CRVS) systems in low- and lower-middle-income countries are failing to provide timely, complete and accurate vital statistics, and it will still be some time before they can provide physician-certified COD for every death. Proposals: Verbal autopsy (VA) is a method to ascertain the probable COD and, although imperfect, it is the best alternative in the absence of medical certification. There is extensive experience with VA in research settings but only a few examples of its use on a large scale. Data collection using electronic questionnaires on mobile devices and computer algorithms to analyse responses and estimate probable COD have increased the potential for VA to be routinely applied in CRVS systems. However, a number of CRVS and health system integration issues should be considered in planning, piloting and implementing a system-wide intervention such as VA. These include addressing the multiplicity of stakeholders and sub-systems involved, integration with existing CRVS work processes and information flows, linking VA results to civil registration records, information technology requirements and data quality assurance. CONCLUSIONS: Integrating VA within CRVS systems is not simply a technical undertaking. It will have profound system-wide effects that should be carefully considered when planning for an effective implementation. This paper identifies and discusses the major system-level issues and emerging practices, provides a planning checklist of system-level considerations and proposes an overview for how VA can be integrated into routine CRVS systems.


Asunto(s)
Autopsia/normas , Causas de Muerte , Programas de Gobierno/organización & administración , Gestión de la Información en Salud/normas , Clasificación Internacional de Enfermedades/normas , Vigilancia de la Población/métodos , Pobreza/estadística & datos numéricos , Humanos , Cooperación Internacional , Encuestas y Cuestionarios , Estadísticas Vitales
19.
Semin Ophthalmol ; 31(4): 358-63, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27100947

RESUMEN

PURPOSE: To review the current literature on socioeconomic disparities relationship with cataract prevalence, characteristics, and management. SUMMARY: Cataracts are an important cause of preventable visual impairment in both the developing and industrialized world. Cataract surgery is a highly effective operation with an excellent risk profile. Furthermore, cataract surgery has been shown to have significant positive functional, social, and economic implications for patients. Several medical conditions have been shown to have correlation with socioeconomic factors and cataract is among several forms of visual impairment that demonstrate this relationship. Disparities in prevalence, clinical characteristics, and management are documented in the ophthalmic literature. A better understanding of these socioeconomic factors and their clinical relevance is critical to alleviating the burden of cataract-related visual impairment in an aging population.


Asunto(s)
Extracción de Catarata/estadística & datos numéricos , Catarata/epidemiología , Disparidades en el Estado de Salud , Clase Social , Extracción de Catarata/economía , Humanos , Prevalencia , Trastornos de la Visión/prevención & control
20.
Semin Ophthalmol ; 31(4): 296-303, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27128153

RESUMEN

Uveal melanoma is the most common intraocular malignancy in adults. Despite excellent rates of local control, half of all patients with uveal melanoma ultimately go on to develop fatal metastatic disease. This review focuses on disparities and differences in the underlying characteristics of the patients, and how these patient characteristics impact the development of metastasis and subsequent patient survival. Specifically, we detail disparities in epidemiology and risk factors as they relate to the development of primary uveal melanoma, to the development of metastasis, and to patient survival following metastasis.


Asunto(s)
Disparidades en el Estado de Salud , Melanoma/epidemiología , Neoplasias de la Úvea/epidemiología , Humanos , Metástasis de la Neoplasia , Factores de Riesgo , Tasa de Supervivencia
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