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1.
Health Educ Res ; 37(1): 36-47, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35134906

RESUMEN

This paper presents results of an impact evaluation of Teen Council, a program that trains youth as peer educators. Teen Council is designed to help peer educators make healthy sexual and reproductive decisions, increase their confidence and abilities to educate their peers and inspire them to advocate for just sexual policies. The program's impact on these educators was evaluated using a randomized controlled trial. Over 5 years, interested high school students in seven states were randomly assigned to a study condition. An intent-to-treat framework using ordinary least square (OLS) regression was employed to measure program effects. Relative to control, Teen Council youth showed enhanced comfort with their own sexuality, greater comfort with and more frequent communication with parents about sexuality and more positive sexual health behaviors, including accessing reproductive health care and adopting more effective means of contraception. Teen Council youth also reported greater confidence in talking with peers about sexuality and more confidence in their civic engagement skills.


Asunto(s)
Embarazo en Adolescencia , Educación Sexual , Adolescente , Femenino , Humanos , Grupo Paritario , Embarazo , Educación Sexual/métodos , Conducta Sexual , Sexualidad
2.
Int J Oral Maxillofac Surg ; 51(6): 768-775, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34924268

RESUMEN

The purpose of this study was to develop a self-administered questionnaire (MRONJ-QoL) to assess the quality of life (QoL) of patients with medication-related osteonecrosis of the jaw (MRONJ). A prospective study was performed to develop and evaluate the questionnaire. The MRONJ-QoL was formulated through a review of the literature and interviews of experts and patients. Following development, it was administered to 60 patients with a diagnosis of MRONJ. The sensibility of the questionnaire was assessed by evaluating feasibility (via interviews of patients), face validity (via interviews of patients and experts), and content validity (via evaluation of internal consistency, floor/ceiling effects, and factor analysis). Reliability was evaluated by measuring intra-rater reliability. Construct validity of the questionnaire was evaluated by both cross-sectional and longitudinal comparisons, including comparing scores of the MRONJ-QoL to disease resolution at 6 months. The final MRONJ-QoL questionnaire consisted of 14 questions, demonstrating high internal consistency (Cronbach's alpha of 0.85) and good reliability (weighted kappa score of 0.65). At the 6-month follow-up, disease resolution was found to be significantly associated with improved MRONJ-QoL scores, suggesting validity of the questionnaire (P < 0.01). Therefore, this is a sensible, reliable, and valid questionnaire for evaluating the QoL of patients with MRONJ.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Estudios Transversales , Humanos , Estudios Prospectivos , Calidad de Vida , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
3.
Water Res ; 174: 115613, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32092546

RESUMEN

Operational and financial constraints challenge effective removal of natural organic matter (NOM), and specifically disinfection by-product (DBP) precursors, at remote and/or small sites. Granular activated carbon (GAC) is a widely used treatment option for such locations, due to its relatively low maintenance and process operational simplicity. However, its efficacy is highly dependent on the media capacity for the organic matter, which in turn depends on the media characteristics. The influence of GAC media properties on NOM/DBP precursor removal has been studied using a range of established and emerging media using both batch adsorption tests and rapid small-scale column tests. DBP formation propensity (DBPFP) was measured with reference to trihalomethanes (THMs) and haloacetic acids (HAAs). All GAC media showed no selectivity for specific removal of precursors of regulated DBPs; DBP formation was a simple function of residual dissolved organic carbon (DOC) levels. UV254 was found to be a good surrogate measurement of DBPFP for an untreated water source having a high DOC. Due to the much-reduced concentration of DBP precursors, the correlation was significantly poorer for the coagulation/flocculation-pretreateed water source. Breakthrough curves generated from the microcolumn trials revealed DOC removal and consequent DBP reduction to correlate reasonably well with the prevalence pores in the 5-10 nm range. A 3-6 fold increase in capacity was recorded for a 0.005-0.045 cm3/g change in 5-10 nm-sized pore volume density. No corresponding correlation was evident with other media pore size ranges.


Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Carbón Orgánico , Desinfección , Trihalometanos
4.
Spinal Cord ; 57(7): 614, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31073233

RESUMEN

A correction to this paper has been published and can be accessed via a link at the top of the paper.

5.
Spinal Cord ; 57(7): 603-613, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30988398

RESUMEN

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe experienced sitting-related health and stability problems among persons with paraplegia (PP) or tetraplegia (TP) and to investigate associations with personal, lesion and wheelchair characteristics as well as satisfaction with sitting posture. SETTING: Dutch community. METHODS: A self-report questionnaire on seating was developed and completed by wheelchair-users living with Spinal Cord Injury (SCI) for ≥10 years (N = 264). Sitting-related problems and satisfaction with sitting posture were compared between participants with PP and TP using Chi-square and t-tests. Logistic regression analyses were performed to investigate associated characteristics. RESULTS: Reported sitting-related problems comprised: sitting to be tiring (regularly to always) (33%), sitting to be painful (28%), pressure ulcers in the last three months (29%), instability while sitting (8%) and instability during reaching (33%). Except for instability during reaching, no differences in occurrence of sitting-problems were found between lesion-group. Persons with TP were more dissatisfied with their sitting posture than persons with PP: 51% vs 36% (p = 0.022) and 51% and 47% respectively thought their sitting posture could be improved (p = 0.670). 'Experienced lack of support in the wheelchair' was associated with most sitting-problems. Pain and instability were associated with dissatisfaction with sitting posture. CONCLUSION: Sitting-related problems and dissatisfaction with sitting posture were frequently reported by persons with long-standing SCI. Sitting problems appeared to associate with lacking support in the wheelchair/seating. A comprehensive feedback from the wheelchair user and a stability check (reach task), as part of the wheelchair/seating-user fitting, may contribute to prevention of sitting-related problems.


Asunto(s)
Paraplejía , Cuadriplejía , Sedestación , Traumatismos de la Médula Espinal , Silla de Ruedas , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paraplejía/complicaciones , Cuadriplejía/complicaciones , Traumatismos de la Médula Espinal/complicaciones , Encuestas y Cuestionarios , Silla de Ruedas/efectos adversos
6.
West Indian med. j ; 67(2): 114-121, Apr.-June 2018. tab
Artículo en Inglés | LILACS | ID: biblio-1045824

RESUMEN

ABSTRACT Objective: The prevalence of sub-dermal contraceptive implant use in Jamaica is low, despite growing international acceptance of long-acting reversible contraception. This study assessed the availability, effectiveness, side-effects and utilization of sub-dermal contraceptive implants and described the characteristics of users over a one-year period. Methods: We reviewed the medical records of women aged 15-45 years who utilized contraceptive implant-related services at any of the six included public health centres in Jamaica during 2013, and surveyed 20 available reproductive healthcare providers. Results: In 2013, 738 women attended a Jamaican public health centre for contraceptive implant services: 493 (66.8%) for insertion, 202 (27.4%) for removal and 53 (7.2%) for follow-up visits (10 women had the same implant inserted and removed in 2013). The women's median age was 26.0 years, 24.3% were ≤ 18 years, and 85.9% had ≥ 1 child. Most women (68.5%) did not have documented side-effects; irregular bleeding, the most commonly documented side-effect, was recorded for 24%. Of the 493 women who had implants inserted, three (0.6%) were identified to be pregnant within three months of insertion. Among the 202 women who had implants removed, 11 (5.4%) experienced complications with removal. Reproductive healthcare providers highlighted the need for an expansion of contraceptive implant availability and provider training. Conclusion: Sub-dermal implants have few insertion complications and side-effects and are effective, but were underutilized in Jamaica. Increased implant availability and enhanced reproductive healthcare provider training may improve implant utilization and reduce unintended pregnancy rates in Jamaica.


RESUMEN Objetivo: La prevalencia del uso de implantes anticonceptivos subdérmicos en Jamaica es baja, a pesar de la creciente aceptación internacional de la anticoncepción reversible de acción prolongada. El presente estudio evalúa la disponibilidad, efectividad, efectos secundarios y utilización de los implantes anticonceptivos subdérmicos, y describe las características de los usuarios durante el período de un año. Métodos: Se revisaron las historias clínicas de mujeres de 15 a 45 años de edad, que utilizaron servicios relacionados con los implantes anticonceptivos en cualquiera de los seis centros de salud pública de Jamaica durante 2013, y se encuestaron 20 profesionales de salud reproductiva disponibles. Resultados: En 2013, 738 mujeres asistieron a un centro de salud pública de Jamaica para recibir servicios de implantes anticonceptivos: 493 (66.8%) para inserción, 202 (27.4%) para eliminación, y 53 (7.2%) para visitas de seguimiento (a 10 mujeres se les insertó y se les quitó el mismo implante en 2013). La edad promedio de las mujeres fue 26.0 años, 24.3% tenían ≤ 18 años, y el 85.9% tenían ≥ 1 niño. La mayoría de las mujeres (68.5%) no presentaban efectos secundarios documentados. El sangramiento irregular - el efecto secundario más comúnmente documentado - se registró en un 24%. De las 493 mujeres que tenían implantes insertados, se halló que tres (0.6%) resultaron embarazadas en el plazo de tres meses tras la inserción. De las 202 mujeres a las que se les había retirado el implante, 11 (5.4%) tuvieron complicaciones en el proceso de la eliminación. Los profesionales de la salud reproductiva destacaron la necesidad de expandir la disponibilidad de implantes anticonceptivos y la capacitación de proveedores. Conclusión: Los implantes subdérmicos presentan pocas complicaciones a la hora de su inserción, y tienen pocos efectos secundarios. Sin embargo, son subutilizados en Jamaica, a pesar de ser efectivos. Una mayor disponibilidad de implantes y una mejor capacitación de los profesionales de la salud reproductiva pueden mejorar la utilización de implantes y reducir las tasas de embarazos no intencionados en Jamaica.


Asunto(s)
Humanos , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anticoncepción Reversible de Larga Duración/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Factores Socioeconómicos , Estudios Retrospectivos , Anticoncepción Reversible de Larga Duración/efectos adversos , Jamaica
7.
Adv Med Educ Pract ; 8: 369-375, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28652840

RESUMEN

PURPOSE: Numerous studies evaluate the use of social media as an open-learning resource in education, but there is a little published knowledge of empirical evidence that such open-learning resources produce educative outcomes, particularly with regard to student performance. This study undertook a systematic review of the published literature in medical education to determine the state of the evidence as to empirical studies that conduct an evaluation or research regarding social media and open-learning resources. METHODS: The authors searched MEDLINE, ERIC, Embase, PubMed, Scopus, and Google Scholar from 2012 to 2017. This search included using keywords related to social media, medical education, research, and evaluation, while restricting the search to peer reviewed, English language articles only. To meet inclusion criteria, manuscripts had to employ evaluative methods and undertake empirical research. RESULTS: Empirical work designed to evaluate the impact of social media as an open-learning resource in medical education is limited as only 13 studies met inclusion criteria. The majority of these studies used undergraduate medical education as the backdrop to investigate open-learning resources, such as Facebook, Twitter, and YouTube. YouTube appears to have little educational value due to the unsupervised nature of content added on a daily basis. Overall, extant reviews have demonstrated that we know a considerable amount about social media use, although to date, its impacts remain unclear. CONCLUSION: There is a paucity of outcome-based, empirical studies assessing the impact of social media in medical education. The few empirical studies identified tend to focus on evaluating the affective outcomes of social media and medical education as opposed to understanding any linkages between social media and performance outcomes. Given the potential for social media use in medical education, more empirical evaluative studies are required to determine educational value.

8.
Water Res ; 112: 226-235, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28167408

RESUMEN

The disinfection by-product (DBP) formation potential (FP) of natural organic matter (NOM) in surface water sources has been studied with reference to the key water quality determinants (WQDs) of UV absorption (UV254), colour, and dissolved organic carbon (DOC) concentration. The data set used encompassed raw and treated water sampled over a 30-month period from 30 water treatment works (WTWs) across Scotland, all employing conventional clarification. Both trihalomethane (THM) and haloacetic acid (HAA) FPs were considered. In addition to the standard bulk WQDs, the DOC content was fractionated and analysed for the hydrophobic (HPO) and hydrophilic (HPI) fractions. Results were quantified in terms of the yield (dDBPFP/dWQD) and the linear regression coefficient R2 of the yield trend. The NOM in the raw waters was found to comprise 30-84% (average 66%) of the more reactive HPO material, with this proportion falling to 18-63% (average 50%) in the treated water. Results suggested UV254 to be as good an indicator of DBPFP as DOC or HPO for the raw waters, with R2 values ranging from 0.79 to 0.82 for THMs and from 0.71 to 0.73 for HAAs for these three determinants. For treated waters the corresponding values were significantly lower at 0.52-0.67 and 0.46-0.47 respectively, reflecting the lower HPO concentration and thus UV254 absorption and commensurately reduced precision due to the limit of detection of the analytical instrument. It is concluded that fractionation offers little benefit in attempting to discern or predict chlorinated carbonaceous DBP yield for the waters across the geographical region studied. UV254 offered an adequate estimate of DBPFP based on a mean yield of ∼2600 and ∼2800 µg per cm-1 absorbance for THMFP for the raw and treated waters respectively and ∼3800 and2900 µg cm-1 for HAAFP, albeit with reduced precision for the treated waters.


Asunto(s)
Trihalometanos/química , Contaminantes Químicos del Agua/química , Desinfección , Purificación del Agua , Abastecimiento de Agua
9.
Eur J Cancer ; 69: 216-222, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27847222

RESUMEN

BACKGROUND: For women with oestrogen receptor+ metastatic breast cancer (MBC), the options for systemic treatment include endocrine therapy (ET) and chemotherapy. For women whose disease is also HER2+, anti-HER2 therapies are also routinely used either with chemotherapy or less commonly with ET. Where chemotherapy is used as initial therapy, treatment is often discontinued due to cumulative toxicity in the absence of disease progression. In this setting, there is the option of introducing ET with the aim of prolonging response and delaying relapse. METHODS: Literature review revealed four trials addressing the question of whether there is a benefit from introducing ET following chemotherapy for MBC. We also sought evidence for alternative approaches, including concurrent chemotherapy and ET and continuing chemotherapy until disease progression. RESULTS: The evidence for the use of ET after chemotherapy in MBC is limited, and the trials done were small. Furthermore, they were performed at a time when both the chemotherapy regimens and ET were different from those used currently. Despite these limitations, there is probably a modest improvement in time to progression for the sequential use of ET after chemotherapy but with no overall survival benefit. An alternative approach, particularly considering agents with relatively low toxicity, such as orally bioavailable fluoropyrimidines, is to continue chemotherapy until disease progression. CONCLUSION: Where chemotherapy for MBC is discontinued due to toxicity, in the absence of progression, the use of ET, with its relatively low toxicity, is a reasonable approach with the aim of delaying relapse.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Acetato de Medroxiprogesterona/uso terapéutico , Tamoxifeno/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Quimioterapia de Mantención , Metástasis de la Neoplasia , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Receptores de Estrógenos/metabolismo , Trastuzumab/uso terapéutico
10.
Sep Sci Technol ; 51(8): 1380-1388, 2016 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-27695148

RESUMEN

The outcomes of a pilot-scale study of the rejection of trihalomethanes (THMs) precursors by commercial ultrafiltration/nanofiltration (UF/NF) spiral-wound membrane elements are presented based on a single surface water source in Scotland. The study revealed the expected trend of increased flux and permeability with increasing pore size for the UF membranes; the NF membranes provided similar fluxes despite the lower nominal pore size. The dissolved organic carbon (DOC) passage decreased with decreasing molecular weight cut-off, with a less than one-third the passage recorded for the NF membranes than for the UF ones. The yield (weight % total THMs per DOC) varied between 2.5% and 8% across all membranes tested, in reasonable agreement with the literature, with the aromatic polyamide membrane providing both the lowest yield and lowest DOC passage. The proportion of the hydrophobic (HPO) fraction removed was found to increase with decreasing membrane selectivity (increasing pore size), and THM generation correlated closely (R2 = 0.98) with the permeate HPO fractional concentration.

11.
J Clin Pharm Ther ; 41(3): 260-5, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26945564

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Midodrine, an orally available α1-agonist indicated for the treatment of orthostatic hypotension, has been used at our institution as an adjunctive treatment to provide haemodynamic support to facilitate intravenous (IV) vasopressor weaning. Limited published data exist for this off-label use; thus, the objective of this study was to evaluate outcomes in patients who received midodrine for IV vasopressor weaning compared to control patients. METHODS: This retrospective comparison included adult ICU patients admitted to our institution from January 2007 to March 2012. The primary outcome was the time to IV vasopressor discontinuation after midodrine initiation. Secondary outcomes included a comparison between midodrine and control patients of the time from IV vasopressor discontinuation to ICU discharge, hospital and ICU length of stay (LOS), and the number of ICU readmissions. RESULTS AND DISCUSSION: The analysis included 188 patients (94 midodrine and 94 control). Patients discontinued IV vasopressors a median of 1·2 days (IQR 0·5-2·8) after midodrine initiation. ICU discharge occurred sooner after IV vasopressor discontinuation (0·8 vs. 1·5 days, P = 0·01), and 96% of patients remained off IV vasopressors after midodrine treatment. Hospital LOS was longer in midodrine patients (P < 0·01), but there were no differences in ICU LOS or readmissions. Adverse event rates after midodrine use were consistent with those observed in other studies. WHAT IS NEW AND CONCLUSION: Midodrine may serve as a useful adjunct to wean IV vasopressors in difficult-to-wean patients. Further studies are needed to assess the efficacy and safety of midodrine for this indication.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Midodrina/administración & dosificación , Vasoconstrictores/administración & dosificación , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Uso Fuera de lo Indicado , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
12.
Int Urogynecol J ; 24(7): 1091-103, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23632798

RESUMEN

INTRODUCTION AND HYPOTHESIS: The objective of this study was to create a valid, reliable, and responsive sexual function measure in women with pelvic floor disorders (PFDs) for both sexually active (SA) and inactive (NSA) women. METHODS: Expert review identified concept gaps and generated items evaluated with cognitive interviews. Women underwent Pelvic Organ Prolapse Quantification (POPQ) exams and completed the Incontinence Severity Index (ISI), a prolapse question from the Epidemiology of Prolapse and Incontinence Questionnaire (ISI scores), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Female Sexual Function Index (FSFI). Principle components and orthogonal varimax rotation and principle factor analysis with oblique rotation identified item grouping. Cronbach's alpha measured internal consistency. Factor correlations evaluated criterion validation. Change scores compared to change scores in other measures evaluated responsiveness among women who underwent surgery. RESULTS: A total of 589 women gave baseline data, 200 returned surveys after treatment, and 147 provided test-retest data. For SA women, 3 subscales each in 2 domains (21 items) and for NSA women 2 subscales in each of 2 domains (12 items) emerged with robust psychometric properties. Cronbach's alpha ranged from .63 to .91. For SA women, correlations were in the anticipated direction with PFDI-20, ISI, and FSFI scores, POPQ, and EPIQ question #35 (all p < .05). PFDI-20, ISI, and FSFI subscale change scores correlated with Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire International Urogynecological Association-revised (PISQ-IR) factor change scores and with mean change scores in women who underwent surgery (all p < .05). For NSA women, PISQ-IR scores correlated with PFDI-20, ISI scores, and with EPIQ question #35 (all p < .05). No items demonstrated differences between test and retest (all p ≥ .05), indicating stability over time. CONCLUSIONS: The PISQ-IR is a valid, reliable, and responsive measure of sexual function.


Asunto(s)
Trastornos del Suelo Pélvico/complicaciones , Prolapso de Órgano Pélvico/complicaciones , Disfunciones Sexuales Fisiológicas/diagnóstico , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Disfunciones Sexuales Fisiológicas/etiología , Encuestas y Cuestionarios
13.
Eye (Lond) ; 27(3): 392-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23258310

RESUMEN

PURPOSE: Demands on publicly funded ophthalmic services worldwide continue to increase with new treatments, waiting time targets, working time limits, and restricted budgets. These highlight the necessity to develop innovative ways of utilising existing capacity more effectively. METHOD: A new regional, fully electronic ophthalmic-referral service with digital imaging was trialled using existing information-technology (IT) infrastructure. Following successful pilot study, the service was rolled out regionally. Service delivery data was prospectively collated for all the attendances in the year prior to (2006) and the year following (2008) introduction. RESULTS: Comparing 2006 against 2008, median waiting times reduced (14 vs 4 weeks), and fewer new patients were observed (8714 vs 7462 P<0.0001), with 1359 referrals receiving electronic diagnosis (e-diagnosis). New patient did not arrive (635 vs 503 P<0.0001) and emergencies also reduced (2671 v 1984 P<0.0001). DISCUSSION: Novel use of existing IT infrastructure improves communication between primary and secondary care. This promotes more effective use of limited outpatient capacity by retaining patients with non-progressive, asymptomatic pathology in the community, whilst fast-tracking patients with sight-threatening disease. Resultant significant, sustained improvements in regional service delivery point to a simple model that could easily be adopted by other providers of universal healthcare globally.


Asunto(s)
Citas y Horarios , Diagnóstico por Imagen , Registros Electrónicos de Salud/organización & administración , Médicos Generales , Oftalmología/organización & administración , Atención Primaria de Salud/organización & administración , Derivación y Consulta/organización & administración , Adulto , Anciano , Femenino , Encuestas de Atención de la Salud , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Proyectos Piloto , Estudios Prospectivos , Programas Médicos Regionales , Medicina Estatal , Telemedicina , Reino Unido , Listas de Espera
14.
Clin Pharmacol Ther ; 90(4): 597-604, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21866096

RESUMEN

The pharmacokinetics (PK), safety, and tolerability of GSK1018921, a glycine transporter 1 (GlyT-1) inhibitor, were assessed in this first-time-in-human (FTIH) study. Single oral doses ranging from 0.5 to 280 mg and placebo were administered to 25 healthy subjects in a five-period, two-cohort, crossover study. GSK1018921 showed dose-proportional PK with a terminal half-life of ~17 h. The subjects reported dizziness with a dose-dependent frequency of 22-88% at doses of 70-280 mg. The time course of the dizziness paralleled the PK of the drug, with peak response at 2 h after the dose, consistent with time to maximum plasma concentration (T(max)). The dizziness was resolved by 10-12 h in all subjects. A Markov-chain logistic regression model was implemented in NONMEM to determine the probability of developing dizziness as a function of the plasma concentration of the compound. Frequency, onset (<1 h), and offset (4 h) were well described by the model. Exposure resulting in 80% receptor occupancy is predicted to be well tolerated.


Asunto(s)
Benzamidas/efectos adversos , Benzamidas/metabolismo , Mareo/inducido químicamente , Mareo/metabolismo , Proteínas de Transporte de Glicina en la Membrana Plasmática/antagonistas & inhibidores , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Pirrolidinas/efectos adversos , Pirrolidinas/metabolismo , Adolescente , Adulto , Estudios de Cohortes , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Adulto Joven
15.
Br J Cancer ; 102(6): 995-1002, 2010 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-20179708

RESUMEN

BACKGROUND: The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab. METHODS: Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented. RESULTS: Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6-24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15-27%) and median TTP was 22 weeks (95% CI: 17-27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P=0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9-39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15-28). CONCLUSIONS: Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Quinazolinas/administración & dosificación , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Capecitabina , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma/patología , Estudios de Cohortes , Desoxicitidina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Genes erbB-2 , Accesibilidad a los Servicios de Salud , Humanos , Lapatinib , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Reino Unido
16.
Eur J Epidemiol ; 22(12): 839-69, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17876711

RESUMEN

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Lípidos/sangre , Albúminas/metabolismo , Biomarcadores/sangre , Enfermedades Cardiovasculares/etiología , Bases de Datos Factuales , Asia Oriental/epidemiología , Humanos , Inflamación/sangre , Recuento de Leucocitos , Lipoproteínas HDL/sangre , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/sangre
18.
Eur J Ophthalmol ; 16(2): 239-46, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16703541

RESUMEN

PURPOSE: To prospectively evaluate the effects of 2% hydroxypropyl-methylcellulose (HPMC-Ophtal) and sodium hyaluronate 1% (Ophthalin) on intraocular pressure, corneal thickness, and endothelial cell loss in small incision cataract surgery with implant. METHODS: A total of 110 patients undergoing routine phacoemulsification with implant received either 2% hydroxypropyl methylcellulose or sodium hyaluronate 1% as ophthalmic viscosurgical device. Pre- and postoperative slitlamp examination, intraocular pressure measurement (preoperatively and at 1-4 hours, 1 day, and 7 days postoperatively), ultrasonic pachymetry (preoperatively and at 1 week, 4-6 weeks, and 12 weeks post operatively), and corneal endothelial cell count (preoperatively and 12 weeks postoperatively) were performed. Data were analyzed using two-way analysis of variance. RESULTS: All measurements were comparable between the two groups preoperatively. Intraocular pressure was significantly lower in the Ophthalin group at 1 day post operatively, while no significant difference was found between the two groups on the 1-4 hours and 7 days examination. The central corneal thickness was not significantly different between the two groups at any postoperative visit . However, the mean cell density demonstrated a significant fall of 11.76% for Ophthalin and 4.27% for HPMC-Ophtal at 12 weeks post-operatively, the difference between the two being significant (p=0.009). CONCLUSIONS: 2% Hydroxypropyl methylcellulose, compared with sodium hyaluronate 1%, is superior in protecting the corneal endothelial cells, has the same effect on central corneal thickness, and is associated with slightly higher intraocular pressure 1 day post operatively. It compares favorably with sodium hyaluronate 1% and can be used as an effective and cheaper alternative in routine small incision cataract surgery with implant.


Asunto(s)
Córnea/anatomía & histología , Endotelio Corneal/efectos de los fármacos , Ácido Hialurónico/farmacología , Presión Intraocular/efectos de los fármacos , Metilcelulosa/análogos & derivados , Facoemulsificación/métodos , Cámara Anterior/efectos de los fármacos , Recuento de Células , Córnea/diagnóstico por imagen , Endotelio Corneal/patología , Humanos , Derivados de la Hipromelosa , Implantación de Lentes Intraoculares , Metilcelulosa/farmacología , Periodo Posoperatorio , Estudios Prospectivos , Ultrasonografía
20.
J Cell Biochem ; 96(1): 97-108, 2005 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-15988762

RESUMEN

Parathyroid hypertensive factor (PHF) is a novel substance secreted by the parathyroid gland (PTG), which is elevated in 30-40% of all hypertensive patients; specifically, the low-renin subset. However, very little is known about the regulation of PHF secretion. Since the classical parathyroid regulator, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), may be elevated concurrent with or preceding the development of low-renin hypertension and elevated plasma PHF, we hypothesized that 1,25-(OH)2D3 would stimulate PHF release. To test this hypothesis, PTG organ and cell cultures, derived from spontaneously hypertensive rats (SHR) and the normotensive genetic control Wistar Kyoto (WKY) rats, were exposed to various vitamin D3 metabolites and PHF release measured by ELISA. 1,25-(OH)2D3 rapidly stimulated PHF release with enhanced sensitivity in SHR versus WKY cultures indicated by a leftward shift in the dose-response curve, whereas 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) had the converse effect. Vitamin D3 analog "BT," an agonist for the classical nuclear vitamin D receptor (1,25VDR(nuc)), was without effect suggesting a 1,25VDR(nuc)-independent mechanism and potential involvement of the plasma membrane-bound vitamin D receptor (1,25 D3-MARRS). Interestingly, protein expression of the 1,25 D3-MARRS was increased in SHR versus WKY parathyroid cells. In conclusion, these results support the idea that 1,25-(OH)2D3 may contribute to elevated plasma PHF in the SHR.


Asunto(s)
24,25-Dihidroxivitamina D 3/fisiología , Factores Biológicos/metabolismo , Calcitriol/fisiología , Colecalciferol/análogos & derivados , Glándulas Paratiroides/metabolismo , Animales , Células Cultivadas , Técnicas de Cultivo de Órganos , Ratas , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo
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