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The synthesis of di- and trisubstituted vinyl fluorides with high isomeric purity remains a challenge for organic synthesis. While many methods exist to access these compounds, the separation of the desired isomer from the minor isomer and/or starting materials often is difficult. Herein, we report a practical method to access di- and trisubstituted vinyl fluorides via a selective Horner-Wadsworth-Emmons olefination/hydrolysis, which provides crystalline 2-fluoroacrylic acids in high (>98%) E-isomeric purity. A subsequent silver-catalyzed stereoretentive decarboxylation provides the title substances with high isomeric purity and without the need for tedious chromatography to remove the minor isomer. The process was amenable to a variety of aldehydes and ketones and provided a diverse array of di- and trisubstituted vinyl fluorides. The sequence was applied to the synthesis of antibacterial and anti-inflammatory compounds.
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In diaspora and transnational studies little is known about the experiences of transnational carer-employees (TCEs). TCEs provide unpaid/informal care across international borders to an adult family member, friend, or relative with disability and/or age-related needs, while also working in paid employment in the country of resettlement. The primary focus of this systematic review was to examine how cultural and historical elements of transnational caregiving influence the economic, social, and health/well-being of TCEs. This systematic review draws on quantitative and qualitative peer-reviewed literature on TCEs' experiences from Canada, the USA, or Australia between 1997 and 2017. In all, 16 articles that fulfilled the search inclusion criteria were selected. The articles were analyzed using content and thematic analysis. The review highlighted that transnational caregiving is a multi-dimensional phenomenon. There is a reciprocal relationship between adult children providing care to their parents and parents helping their children resettle in their new home. The findings suggest that TCEs provide practical, financial, and emotional care to their families abroad. To the best of our knowledge, this is the first comprehensive systematic review of the experiences of TCEs. Increasingly complex immigration experiences of transnational families require innovative policy responses from a transnational and intersectionality lens. Immigrants need support to maintain solid transnational networks and simultaneously adapt to the country of resettlement. Employers can use the findings to support TCEs in balancing unpaid care across vast geographical distances while sustaining their economic and social well-being.
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Cuidadores , Padres , Humanos , Cuidadores/psicología , Familia/psicología , Canadá , EmpleoRESUMEN
INTRODUCTION: Evidence indicates that assistance dogs placed in the home are effective in supporting individuals with Autism Spectrum Disorder (ASD) by increasing social and community participation and promoting quality of life. This study aimed to examine the outcomes of assistance dog placement on quality of life, independence, and participation of families including individuals with ASD placed with an assistance dog compared to families on the waiting list for an autism assistance dog and to evaluate the feasibility of the design for future studies. METHODS: A cross-sectional comparative study was conducted. The Adaptive Behaviour Analysis System, Social Responsiveness Scale, Autism Treatment Evaluation Checklist, Canadian Occupational Performance Measure, and Autism Family Experience Questionnaire were used to evaluate adaptive skills, behaviour, social difficulties, daily functioning, and family quality of life. RESULTS: Six families who had an autism assistance dog placed with them, and 12 families who were on the waiting list were recruited using purposeful sampling. The pilot data found no significant differences between the two groups. However, trends were observed which suggested that assistance dogs can increase desired social behaviours, decrease ASD severity, and improve family wellbeing. For families with an assistance dog, more positive outcomes were observed for families who were partnered with an assistance dog for longer. Parents (and sometimes individuals with ASD) were able to complete and return the outcome measures via mail to collect the outcome data for the study. CONCLUSION: These study findings add to the developing evidence about the use of assistance dogs with this population. A larger sample size may have allowed for significant associations to be detected. The methods used were feasible to be applied in a larger study. These results may assist health professionals advocate for funding for assistance dog placement to individuals with ASD and their families.
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Trastorno del Espectro Autista , Terapia Ocupacional , Animales , Trastorno del Espectro Autista/terapia , Canadá , Estudios Transversales , Perros , Humanos , Proyectos Piloto , Calidad de Vida , Animales de ServicioRESUMEN
Autodissemination techniques can potentially be used to distribute insecticides, including microbial insecticides, to cryptic pests. This approach is reliant on the target insect either passing the pathogen passively to other insects or the pathogen cycling within the population after the initial host dies. Here we examine, in small scale experiments, whether male Agriotes obscurus click beetles passively transmit the spores of the fungus Metarhizium brunneum directly, or indirectly via the environment, and whether this is influenced by exposure to synthetic female pheromone. We found that the beetles did not avoid M. brunneum spores and that this behaviour was not affected by pheromone. Exposure to pheromone increased beetle movement and uptake of spores, but this did not result in an increase in infected beetles under our conditions. Beetles were able to transfer spores at high levels via environmental contamination. However, contamination of the environment declined rapidly after exposure to the spores. The results are discussed in the context of developing an autodissemination strategy for click beetles.
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Escarabajos/fisiología , Metarhizium/fisiología , Atractivos Sexuales/farmacología , Animales , Escarabajos/microbiología , Femenino , Masculino , Control Biológico de VectoresRESUMEN
IMPORTANCE: Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long-term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong. PARTICIPANTS: A total of 80 Chinese participants, aged 18 or above, with T2DM recruited from the specialist outpatient setting were included. METHODS: The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI). The association between OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using multiple linear regression. MAIN OUTCOME MEASURES: The associations between long-term glycaemic control and NITBUT and OSDI scores. RESULTS: Stepwise multiple linear regression analysis revealed glycated haemoglobin to be the only significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2 = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM population. The odds of DES for increasing percentage of glycated haemoglobin was 1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE: Our findings highlight the importance of good glycaemic control as a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Síndromes de Ojo Seco/diagnóstico , Hemoglobina Glucada/metabolismo , Lágrimas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Córnea/metabolismo , Córnea/patología , Topografía de la Córnea , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Síndromes de Ojo Seco/epidemiología , Síndromes de Ojo Seco/etiología , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
BACKGROUND: Compliance with maternity clinical practice guidelines developed by National Women's Health has been found to be low at audit. OBJECTIVE: To explore the reasons for poor compliance with maternity guidelines by evaluating the quality of a sample of National Women's Health guidelines using a validated instrument and assessing local guideline users' perceptions of and attitudes toward guidelines. DESIGN: Five independent reviewers evaluated the quality of 10 purposively selected guidelines for adherence to the Appraisal of Guidelines Research & Evaluation (AGREE) II instrument standards. A self-administered questionnaire for staff was undertaken regarding views of and barriers to guideline use. RESULTS: None of the guidelines attained a score over 50% for the following domains: stakeholder involvement, rigour of development, applicability, editorial independence. The highest scoring domain was clarity of presentation (mean 69%). All guidelines scored the minimum possible for editorial independence. Survey respondents had positive attitudes toward guidelines, believed that their use could improve quality of care within the service, and felt that encouragement from senior staff members and peers would encourage their use. Accessibility was the most commonly cited of many barriers identified. CONCLUSION: The National Women's Health guidelines evaluated in this study cannot be considered to be high quality, and could be improved by reporting on methodology of the development process. Although poor guideline development may contribute to failure of the local maternity guidelines, it appears that accessibility is a major barrier to their use and implementation.
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Actitud del Personal de Salud , Salas de Parto , Adhesión a Directriz , Cuerpo Médico de Hospitales , Partería , Guías de Práctica Clínica como Asunto/normas , Conocimientos, Actitudes y Práctica en Salud , Humanos , Encuestas y Cuestionarios , Centros de Atención TerciariaRESUMEN
Described herein is a synthetic strategy for the total synthesis of (±)-phomoidrideâ D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.
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Anhídridos Maleicos/síntesis química , Compuestos Bicíclicos con Puentes/química , Ciclización , Reacción de Cicloadición , Oxidación-Reducción , EstereoisomerismoRESUMEN
Aneurysmal subarachnoid hemorrhage (SAH) is a serious disease with high case fatality and morbidity. Early cerebral infarction has been suggested as a risk factor for poor outcome. We aimed to assess the pattern of early and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage. We prospectively enrolled consecutive aneurysmal subarachnoid hemorrhage (SAH) patients presenting to an academic neurosurgical referral center (Prince of Wales Hospital, the Chinese University of Hong Kong) in Hong Kong. Cerebral infarction occurred in 24 (48 %) patients, in which 14 (28 %) had early cerebral infarction and 14 (28 %) had delayed cerebral infarction. Early anterior cerebral infarction occurred in a similar proportion of anterior and posterior circulation aneurysms (24 % vs. 21 %), whereas posterior circulation aneurysm patients had a higher proportion of early posterior cerebral infarction compared with anterior circulation aneurysm patients (18 % vs. 2 %). In conclusion, early cerebral infarction was common and different from delayed cerebral infarction.
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Infarto Cerebral/epidemiología , Hemorragia Subaracnoidea/epidemiología , Adulto , Infarto Encefálico , Infarto Cerebral/diagnóstico por imagen , Estudios de Cohortes , Progresión de la Enfermedad , Procedimientos Endovasculares , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Procedimientos Neuroquirúrgicos , Estudios Prospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/cirugía , Instrumentos Quirúrgicos , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: The aim of this study was to investigate the effect of an upright position on cerebellar tonsillar level in patients with adolescent idiopathic scoliosis (AIS). METHODS: Twenty-five patients with clinically diagnosed AIS and 18 normal controls were examined in both supine and upright positions using 0.25T MRI. The position of the inferior cerebellar tonsil tip relative to a reference line connecting the basion to the opisthion (BO line) was measured in millimetres. RESULTS: None of the 18 normal control subjects had cerebellar tonsillar descent below the BO line in either supine or the upright position. Forty-eight percent of AIS patients had tonsillar descent in the upright position, compared to 28 % in the supine position. In the upright position, cerebellar tonsillar position was lower in AIS patients than in normal subjects (mean -0.7 ± 1.5 vs. +2.1 ± 1.7, p < 0.00001). AIS patients also had a large degree of tonsillar excursion between upright and supine positions compared to normal subjects (mean -1.9 ± 2.3 vs. -0.1 ± 0.2, p < 0.00001). CONCLUSIONS: When considering the theoretical likelihood that a low tonsillar position may affect spinal cord function, one should bear in mind that tonsillar descent in AIS is significantly greater in the upright position. KEY POINTS: ⢠AIS patients exhibited greater cerebellar tonsillar descent in upright than supine position. ⢠Cerebellar tonsillar position was lower in AIS patients than normal subjects. ⢠AIS patients exhibited greater tonsillar excursion between supine and upright positions.
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Cerebelo/patología , Postura/fisiología , Escoliosis/patología , Adolescente , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Estudios Prospectivos , Médula Espinal/fisiologíaRESUMEN
BACKGROUND & AIMS: Little is known about the validity of hepatocellular carcinoma (HCC) risk scores derived from treatment-naïve patients with chronic hepatitis B for patients treated with entecavir. METHODS: We performed a retrospective-prospective cohort study of 1531 patients with chronic hepatitis B (age, 51 ± 12 years; 1099 male; 332 with clinical cirrhosis) who were treated with entecavir 0.5 mg daily for at least 12 months at Prince of Wales Hospital in Hong Kong from December 2005 to August 2012. The patients were assessed once every 3 to 6 months for symptoms, drug history, and adherence; blood samples were collected for biochemical analyses. We validated 3 HCC risk scores (CU-HCC, GAG-HCC, and REACH-B scores) based on data collected when patients began treatment with entecavir and 2 years later. RESULTS: After 42 ± 13 months of follow-up, 47 patients (2.9%) developed HCC. The 5-year cumulative incidence of HCC was 4.3% (95% confidence interval [CI], 3.6%-5.0%). Older age, presence of cirrhosis, and virologic remission after 24 months or more of therapy were independently associated with HCC in the entire cohort; advanced age and hypoalbuminemia were associated with HCC in patients without cirrhosis. The area under the receiver operating characteristic curves (AUCs) for baseline CU-HCC, GAG-HCC, and REACH-B scores for HCC were 0.80 (95% CI, 0.75-0.86), 0.76 (95% CI, 0.70-0.82), and 0.71 (95% CI, 0.62-0.81), respectively; the time-dependent AUCs 1 to 4 years after patients started treatment were comparable to those at baseline. The cutoff value of the baseline CU-HCC score identified patients who would develop HCC with 93.6% sensitivity and 47.8% specificity, the baseline GAG-HCC score with 55.3% sensitivity and 78.9% specificity, and the baseline REACH-B score with 95.2% sensitivity and 16.5% specificity. Compared with patients with CU-HCC scores <5 at baseline, those with CU-HCC scores that either decreased from ≥5 to <5 or remained ≥5 had a higher risk of HCC (5-year cumulative incidences, 0% vs 3.9% and 7.3%; P = .002 and P < .001, respectively). CONCLUSIONS: The CU-HCC, GAG-HCC, and REACH-B HCC risk scores accurately predict which patients with chronic hepatitis B treated with entecavir will develop HCC.
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Carcinoma Hepatocelular/epidemiología , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Medición de Riesgo/métodos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Carcinoma Hepatocelular/etiología , Intervalos de Confianza , ADN Viral/análisis , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Guanina/administración & dosificación , Guanina/efectos adversos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Hong Kong/epidemiología , Humanos , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Polineuropatías/inducido químicamente , Polineuropatías/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Vincristina/efectos adversos , Antineoplásicos Fitogénicos/efectos adversos , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Radiofármacos , Imagen de Cuerpo EnteroRESUMEN
UNLABELLED: Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first-line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective-prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5-year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver-related mortality. A total of 1,446 entecavir-treated patients (72% men; age, 51 ± 12 years; follow-up, 36 ± 13 months) and 424 treatment-naïve patients (65% men; age, 41 ± 13 years; follow-up, 114 ± 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir-treated, 69 treatment-naïve), entecavir-treated patients had reduced risks of all clinical outcomes when compared with treatment-naïve patients with cirrhosis after adjusted for model for end-stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34-0.78; P = 0.002), HCC (HR, 0.55; 95% CI, 0.31-0.99; P = 0.049), liver-related mortality (HR, 0.26; 95% CI, 0.13-0.55; P < 0.001), and all-cause mortality (HR, 0.34; 95% CI, 0.18-0.62; P < 0.001). Entecavir-treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients. CONCLUSION: Entecavir therapy reduces the risks of hepatic events, HCC, liver-related and all-cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression.
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Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Cirrosis Hepática/virología , Adulto , Anciano , Carcinoma Hepatocelular/prevención & control , ADN Viral/sangre , Femenino , Guanina/uso terapéutico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/mortalidad , Hepatitis B Crónica/virología , Humanos , Neoplasias Hepáticas/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVES: We aimed to assess the safety and efficacy of sonographically guided high-intensity focused ultrasound for treating patients with symptomatic uterine fibroids using a modified protocol. METHODS: This work was part of an ongoing prospective phase 1 study. Twenty patients with 22 symptomatic fibroids were treated with sonographically guided high-intensity focused ultrasound under no anesthesia. The modified protocol consisted of repeated and shortened (<25 minutes) treatment sessions of high-input acoustic intensity (1000-1500 W/cm(2)) and intensified sonication pulses (1500-2000) at each spot. The primary end points were periprocedural complications. The secondary end points were symptomatic improvement and radiologic evidence of treatment responses, including the degree of fibroid infarction and volume shrinkage 3 months after treatment. Symptomatic improvement was assessed by a pain score, a pictorial chart menstrual score, the Urogenital Distress Inventory short form, and the Incontinence Impact Questionnaire short form. The degree of fibroid infarction was assessed by the nonperfused ratio on contrast-enhanced magnetic resonance imaging, defined as the ratio of the nonperfused fibroid volume to the total fibroid volume. RESULTS: Nineteen patients tolerated the treatment well, with no major adverse events. One patient who received treatment for a fibroid located within 6 cm from the skin had third-degree skin burns at 2 sites of 1 cm in diameter. Fibroid-related abdominal pain, pictorial chart, Urogenital Distress Inventory, and Incontinence Impact Questionnaire scores were significantly improved (P < .05). The median nonperfused ratio at 3 months was 20% (95% confidence interval, 5%-32.5%). Median volume shrinkage at 3 months was 17.2% (95% confidence interval, 4.3%-26.6%). CONCLUSIONS: Sonographically guided high-intensity focused ultrasound using a modified protocol may be safe and effective for symptomatic uterine fibroids in selected patients to avoid skin burns.
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Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Leiomioma/cirugía , Neoplasias Uterinas/cirugía , Adulto , Medios de Contraste/administración & dosificación , Femenino , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Humanos , Leiomioma/patología , Imagen por Resonancia Magnética , Meglumina/administración & dosificación , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Dimensión del Dolor , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Intervencional , Neoplasias Uterinas/patologíaRESUMEN
Despite the availability of a wide range of contraceptive options in Australia, rates of unintended pregnancy remain high. A survey of tertiary students in Far North Queensland in regard to their knowledge of contraceptive methods and services revealed significant deficiencies, suggesting that existing sex education and contraceptive advice services need improving if unplanned pregnancy rates are to be reduced in this population.
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Conducta Anticonceptiva/estadística & datos numéricos , Anticoncepción/métodos , Anticonceptivos Orales Combinados/uso terapéutico , Conocimientos, Actitudes y Práctica en Salud , Estudiantes/psicología , Condones/estadística & datos numéricos , Anticonceptivos Orales Combinados/efectos adversos , Anticonceptivos Sintéticos Orales/uso terapéutico , Servicios de Planificación Familiar , Femenino , Humanos , Conducta en la Búsqueda de Información , Dispositivos Intrauterinos/estadística & datos numéricos , Masculino , Medroxiprogesterona/uso terapéutico , Queensland , Abstinencia Sexual , Enfermedades de Transmisión Sexual/prevención & control , Esterilización/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Pathological fracture is an uncommon presentation in patients with long bone osteosarcoma. PROCEDURES: We retrospectively reviewed the database of all patients with histologically proven osteosarcoma under the age of 18 years from 1991 to 2011 in a tertiary pediatric oncology referral center. Five patients with pathological fractures as the first presentation of osteosarcoma were identified. The treatment strategies and complications were evaluated. Ten sex-, age-, and site- matched osteosarcoma patients without pathological fracture were selected as controls. The incidence of distant metastases and outcome, including local recurrence and survival, were compared between the index (with pathological fracture) and the control (without pathological fracture) groups. RESULTS: In the index group, all five patients were boys and the mean age of onset was 13.1 years (range 9.2-14.9). Three patients (60%, 3/5) received amputation and two (40%) had wide local excision of the tumor. Pathological fracture group showed higher rate of lung (60% vs. 10%, P = 0.04) and bone (60% vs. 10%, P = 0.04) metastases at presentation, and shorter overall 5-year survival (P = 0.04) than the control group. There was no significant difference of local recurrence (20%, P = 1.00) between these two groups regardless of the type of operation. CONCLUSION: Osteosarcoma complicated by pathological fracture as first presentation had higher incidence of lung and bone metastases at presentation and worse survival rate when compared with patients without pathological fracture.
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Neoplasias Óseas/complicaciones , Fracturas Óseas/etiología , Osteosarcoma/complicaciones , Osteosarcoma/secundario , Adolescente , Neoplasias Óseas/epidemiología , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Niño , Femenino , Fracturas Óseas/epidemiología , Humanos , Incidencia , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/secundario , Masculino , Osteosarcoma/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The ruthenium catalyst generated in situ from Ru(3)(CO)(12) and tricyclohexylphosphine, PCy(3), promotes the redox-neutral C-C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C-H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C-C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene-carbonyl oxidative coupling.
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Metanol/química , Prenilación , Rutenio/química , Catálisis , Ésteres , Espectroscopía de Resonancia Magnética , Oxidación-ReducciónRESUMEN
Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1 b and aldehydes 3 a-3 l engage in reductive coupling to provide products of propargylation 4 a-4 l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1 b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4 f-h and 4 k to 5 f-h and 5 k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.
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Aldehídos/química , Alquinos/química , Alquinos/síntesis química , Propanoles/química , Propanoles/síntesis química , Rutenio/química , Catálisis , Hidrogenación , Estructura Molecular , Oxidación-Reducción , EstereoisomerismoRESUMEN
BACKGROUND: Despite the known safety risks of long-term use of sedative-hypnotic/anxiolytic medications, there has been limited guidance for the safe and effective use of their chronic use in a primary care clinic setting. Understanding the characteristics of patients who receive sedative-hypnotic/anxiolytic medication and the clinical documentation process in primary care is the first step towards understanding the nature of the problem and will help inform future strategies for clinical research and practice. OBJECTIVES: Characterize patients who received a sedative-hypnotic/anxiolytic prescription in primary care, and (2) gain an understanding of the clinical documentation of sedative-hypnotic/anxiolytic indication and monitoring in electronic medical records (EMR). METHODS: A random selection of patients who received a prescription for a benzodiazepine or Z-drug hypnotic between January 2014 and August 2016 from four primary care clinics in Winnipeg were included. Data was collected retrospectively using the EMR (Accuro®). Patient variables recorded included sex, age, comorbidities, medications, smoking status, and alcohol status. Treatment variables included drug type, indication, pattern of use, dose, adverse events, psychosocial intervention, tapering attempts, social support, life stressor, and monitoring parameters for sedative-hypnotic use. Demographic and clinical characteristics were described using descriptive statistics. RESULTS: Records from a sample of 200 primary care patients prescribed sedative-hypnotic/anxiolytics were analyzed (mean age 55.8 years old, 61.5% ≥ 65 years old, 61.0% female). Long-term chronic use (≥ 1 year) of a sedative-hypnotic/anxiolytic agent was observed in 29.5% of the sample. Zopiclone (30.7%) and lorazepam (28.7%) were the most common agents prescribed. Only 9.5% of patients had documentation of a past tapering attempt of their sedative-hypnotic/anxiolytic. The most common indications for sedative-hypnotic/anxiolytic use recorded were anxiety (33.0%) and sleep (18.0%), but indication was undetermined for 57.0% of patients. Depression (33.5%) and falls (18.5%) were reported by patients after the initiation of these agents. CONCLUSIONS: A higher proportion of females and users 65 years and older received a prescription for a sedative-hypnotic/anxiolytic, consistent with previous studies on sedative-hypnotic use. We found inconsistencies in the documentation surrounding sedative-hypnotic/anxiolytic use. The indication for their use was unclear in a large number of patients. These findings will help us understand the state of the problem in primary care and inform future strategies for clinical research.
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Ansiolíticos , Anciano , Ansiolíticos/efectos adversos , Documentación , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios RetrospectivosRESUMEN
Under the conditions of ruthenium-catalyzed transfer hydrogenation, 1,1-disubstituted allenes 1a-c and alcohols 2a-g engage in redox-triggered generation of allylruthenium-aldehyde pairs to form products of hydrohydroxyalkylation 3a-g, 4a-g, and 5a-g with complete branched regioselectivity. By exploiting Curtin-Hammett effects, good to excellent levels of anti-diastereoselectivity (4:1 to >20:1) are obtained. Thus, all carbon quaternary centers are formed in a diastereoselective fashion upon carbonyl addition from the alcohol oxidation level in the absence of premetalated nucleophiles or stoichiometric byproducts. Exposure of allene 1b to equimolar quantities of alcohol 2a and aldehyde 6b under standard reaction conditions delivers adducts 4a and 4b in a 1:1 ratio. Similarly, exposure of allene 1b to equimolar quantities of aldehyde 6a and alcohol 2b provides adducts 4a and 4b in an identical equimolar ratio. Exposure of allene 1b to d(2)-p-nitrobenzyl alcohol, deuterio-2a, under standard reaction conditions delivers the product of hydrohydroxyalkylation, deuterio-4a, which incorporates deuterium at the carbinol position (>95% (2)H) and the interior vinylic position (34% (2)H). Competition experiments involving exposure of allene 1b to equimolar quantities of benzylic alcohols 2a and deuterio-2a reveal no significant kinetic effect. The collective data corroborate rapid, reversible alcohol dehydrogenation, allene hydrometalation, and (E)-, (Z)-isomerization of the transient allylruthenium in advance of turnover-limiting carbonyl addition. Notably, analogous allene-aldehyde reductive C-C couplings employing 2-propanol as the terminal reductant display poor levels of anti-diastereoselectivity, suggesting that carbonyl addition is not turnover-limiting in reactions conducted from the aldehyde oxidation level.
Asunto(s)
Alcadienos/química , Carbono/química , Rutenio/química , Alquilación , Catálisis , Oxidación-Reducción , Estereoisomerismo , Especificidad por SustratoRESUMEN
Nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to a variety of aldehydes under the conditions of ruthenium-catalyzed transfer hydrogenation by employing formic acid as the terminal reductant and delivering the products of carbonyl vinylation with good to excellent levels of regioselectivity and with complete control of olefin stereochemistry. As revealed in an assessment of the ruthenium counterion, iodide plays an essential role in directing the regioselectivity of C-C bond formation. Isotopic labeling studies corroborate reversible catalytic propargyl C-H oxidative addition in advance of the C-C coupling, and demonstrate that the C-C coupling products do not experience reversible dehydrogenation by way of enone intermediates. This transfer hydrogenation protocol enables carbonyl vinylation in the absence of stoichiometric metallic reagents.