RESUMEN
BACKGROUND: Infraorbital nerve blocks are often performed for the management of postoperative pain associated with cleft lip correction. Infraorbital nerve block procedures depend on the identification of the infraorbital foramen; however, there is little information regarding the infraorbital foramen location in the pediatric population. AIMS: The aim of this study was to identify the location of the infraorbital foramen in the pediatric population relative to a midpoint between the nasospinale and jugale. METHODS: The study assessed the location of 152 infraorbital foramina relative to a midpoint between the nasospinale and J on dry crania. Crania were from individuals ranging in age-at-death from 6-month fetal to 18 years. The population was subdivided into fetal/infant (≥6 months fetal age-<2 years), child (≥2-<12 years), and adolescent (≥12-≤18 years) groups for comparison. RESULTS: The average distance of the infraorbital foramen from the nasospinale-to-jugale midpoint was 1.55 ± 0.78 mm (Mean ± SD) in the fetal/infant group, 0.80 ± 0.91 mm in the child group, and 1.31 ± 1.68 mm in the adolescent group. Furthermore, infraorbital foramina tended to be located medial to the nasospinale-to-jugale midpoint in the fetal/infant population, directly upon or superomedial to the nasospinale-to-jugale midpoint in the child population, and directly upon or superior/superolateral to the nasospinale-to-jugale midpoint in the adolescent population. CONCLUSIONS: The infraorbital foramen was located within 2 mm, on average, from the nasospinale-to-jugale midpoint regardless of age group. Therefore, the nasospinale-to-jugale midpoint may serve as useful means of identifying the location of the infraorbital foramen in the pediatric population and aid in optimizing infraorbital nerve block procedures. The information in this report is valuable in general, but may be particularly useful in developing countries where there is a lack of ultrasound training and availability for health care providers; or places where infraorbital nerve block may be the sole anesthetic modality for cleft lip surgery, even among adolescent patients.
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Bloqueo Nervioso/métodos , Órbita/anatomía & histología , Órbita/inervación , Adolescente , Niño , Preescolar , Humanos , LactanteRESUMEN
Identification of the infraorbital foramen is important in infraorbital nerve block and the prevention of iatrogenic injury of the infraorbital nerve in maxillofacial surgeries. This study assessed the location of 887 infraorbital foramina from 518 adult crania of varied sex and population. The study assessed the midpoint of a line segment spanning from nasospinale to jugale (NS-J) relative to the infraorbital foramen. The mean distance of the NS-J midpoint from the infraorbital foramen was 2.1â±â1.9âmm (meanâ±âSD) with a mode of 0âmm (266:887; 30%). The NS-J midpoint was located in the same plane or inferior to the infraorbital foramen in 98.4% of sides (873:887). There were no significant differences between sexes, populations, or sides with regard to the NS-J midpoint to infraorbital foramen distance. The NS-J midpoint can be used to locate the infraorbital foramen in both females and males of varied populations regardless of craniofacial diversity. The results of this study will aid in infraorbital nerve block procedures and maxillofacial surgery.
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Bloqueo Nervioso , Órbita/anatomía & histología , Procedimientos Quirúrgicos Ortognáticos , Adulto , Femenino , Humanos , Masculino , Órbita/inervación , Factores SexualesRESUMEN
Metopism, the persistence of the metopic suture in adulthood, is a clinically significant radiographic finding. In addition to masquerading as a fracture of the frontal bone, a persistent metopic suture may be associated with other clinically significant anatomical variations including frontal sinus abnormalities. Several geographically and craniofacially distinct populations have yet to be assessed for the prevalence of metopism. This study aimed to determine the prevalence of metopic sutures in adult crania of diverse populations among which scant research exists. A total of 505 adult crania were examined for the presence of a metopic suture. A total of 13 (2.57%) demonstrated metopism. Among subpopulations, metopism was present in 8.06% (5:62) of European crania, 15.38% (2:13) of East Asian crania, 2.20% (2:91) of Egyptian crania, and 2.86% (1:35) of Bengali crania. Metopism was also found in 1 Chilean, Roman, and Tchuktchi cranium, respectively. Metopism was not seen in crania from individuals of African (non-Egyptian) descent (0:62), Peruvians (0:144), Malayans (0:23), or Mexicans (0:23). Among sexes, metopism was present in 3.77% (8:212) of females and 1.79% (5:279) of males. The prevalence of metopism differs between populations and sexes. The results of this study provide anthropological, developmental, and clinical insight with regard to metopism.
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Suturas Craneales/anomalías , Anomalías Craneofaciales/etnología , Hueso Frontal/anomalías , Adulto , Asia/etnología , Chile/etnología , Egipto/etnología , Europa (Continente)/etnología , Femenino , Humanos , Masculino , México/etnología , Perú/etnología , PrevalenciaRESUMEN
Tuberculosis (TB) is a contagious bacterial disease of global concern. During 2013, an estimated nine million incident TB cases occurred worldwide (1). The majority (82%) were diagnosed in 22 countries, including South Africa and the Philippines, where annual incidence was 860 TB cases per 100,000 persons and 292 TB cases per 100,000 persons, respectively (1). The 2013 TB incidence in the United States was three cases per 100,000 persons (2). Under the Immigration and Nationality Act, TB screening is required for persons seeking permanent residence in the United States (i.e., immigrants and refugees), but it is not routinely required for nonimmigrants who are issued temporary visas for school or work (3). A portion of the U.S. tourism industry relies on temporary visa holders to accommodate seasonal and fluctuating demand for service personnel (4). This report describes three foreign-born persons holding temporary visas who had infectious TB while working at tourist destinations in the United States during 2012-2014. Multiple factors, including dormitory-style housing, transient work patterns, and diagnostic delays might have contributed to increased opportunity for TB transmission. Clinicians in seasonally driven tourist destinations should be aware of the potential for imported TB disease in foreign-born seasonal workers and promptly report suspected cases to health officials.
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Empleo/estadística & datos numéricos , Personal Profesional Extranjero/estadística & datos numéricos , Industrias , Tuberculosis/diagnóstico , Adulto , Emigración e Inmigración/legislación & jurisprudencia , Femenino , Humanos , Incidencia , Masculino , Tamizaje Masivo/legislación & jurisprudencia , Persona de Mediana Edad , Filipinas/etnología , Sudáfrica/etnología , Tuberculosis/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The Age, Blood pressure, Clinical features, Duration of symptoms, Diabetes (ABCD2) score can be used to predict early recurrent stroke risk following Transient ischemic attack (TIA). Given that recurrent stroke risk can be as high as 20% in the first week, international guidelines recommend "high-risk" TIAs (ABCD2 >3) be seen by specialist services such as dedicated acute neurovascular clinics within 24 hours. The goal of this study was to examine the associations of both quality of referrals to a specialist acute clinic and of "guideline congruence" of time-to-clinic consultation after TIA/minor stroke. We hypothesized high-quality referrals containing key clinical elements would be associated with greater guideline congruence. METHODS: A retrospective analysis of referrals to an acute neurovascular clinic within a tertiary care hospital of consecutive patients with TIA/minor stroke. Quality of general practitioner and emergency department referrals was defined on the basis of information content enabling ABCD2-based risk stratification by the clinic triage service. Time-to-clinic consultation was used to define "guideline congruence." RESULTS: Referrals of 148 consecutive eligible patients were reviewed. Sixty-six percent of cases were subsequently neurologist-diagnosed as TIA or minor stroke. Seventy-nine percent were referred by general practitioners. Fifty-three percent of referrals were of high quality, but quality was not associated with guideline congruence. Of the high-risk patients, only 3.6% were seen at the clinic within 24 hours of index event and 31.3% within 24 hours of referral. CONCLUSIONS: Current guidelines are pathophysiologically logical and evidence based, but are difficult to implement. Improving quality of primary-secondary communication by improved referral quality is unlikely to improve guideline compliance. Alternative strategies are needed to reduce recurrent stroke risk after TIA/minor stroke.
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Adhesión a Directriz/normas , Cooperación del Paciente , Derivación y Consulta/normas , Accidente Cerebrovascular/terapia , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tiempo de TratamientoRESUMEN
For more than two decades, as the number of tuberculosis (TB) cases overall in the United States has declined, the proportion of cases among foreign-born persons has increased. In 2013, the percentage of TB cases among those born outside the country was 64.6%. To address this trend, CDC has developed strategies to identify and treat TB in U.S.-bound immigrants and refugees overseas. Each year, approximately 450,000 persons are admitted to the United States on an immigrant visa, and 50,000-70,000 are admitted as refugees. Applicants for either an immigrant visa or refugee status are required to undergo a medical examination overseas before being allowed to travel to the United States. CDC is the federal agency with regulatory oversight of the overseas medical examination, and panel physicians appointed by the U.S. Department of State perform the examinations in accordance with Technical Instructions (TI) provided by CDC's Division of Global Migration and Quarantine (DGMQ). Beginning in 1991, the algorithm for TB TI relied on chest radiographs for applicants aged ≥15 years, followed by sputum smears for those with findings suggestive of TB; no additional diagnostics were used. In 2007, CDC issued enhanced standards for TB diagnosis and treatment, including the addition of sputum cultures (which are more sensitive than smears) as a diagnostic tool and treatment delivered as directly observed therapy (DOT). This report summarizes worldwide implementation of the new screening requirements since 2007. In 2012, the year for which the most recent data are available, 60% of the TB cases diagnosed were in persons with smear-negative, but culture-positive, test results. The results demonstrate that rigorous diagnostic and treatment programs can be implemented in areas with high TB incidence overseas.
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Emigrantes e Inmigrantes/legislación & jurisprudencia , Tamizaje Masivo/legislación & jurisprudencia , Desarrollo de Programa , Refugiados/legislación & jurisprudencia , Tuberculosis/diagnóstico , Adolescente , Centers for Disease Control and Prevention, U.S. , Niño , Preescolar , Farmacorresistencia Microbiana , Emigración e Inmigración/estadística & datos numéricos , Humanos , Ensayos de Liberación de Interferón gamma , Tamizaje Masivo/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Guías de Práctica Clínica como Asunto , Esputo/microbiología , Prueba de Tuberculina , Tuberculosis/epidemiología , Tuberculosis/terapia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. FINDINGS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). INTERPRETATION: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. FUNDING: Australian National Health Medical Research Council; Boehringer Ingelheim.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Imagen de Perfusión , Tenecteplasa , Activador de Tejido Plasminógeno , Humanos , Tenecteplasa/uso terapéutico , Tenecteplasa/administración & dosificación , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Persona de Mediana Edad , Imagen de Perfusión/métodos , Terapia Trombolítica/métodos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
To determine whether immediate post-operative brachytherapy can be safely applied to newly diagnosed glioblastomas to retard tumor progression prior to initiation of external beam radiation therapy (EBRT) and temozolomide. Between 1996 and 2011, eleven patients underwent implantation of GliaSite (n = 9) or MammoSite (n = 2) at the time of surgical resection. Brachytherapy was carried out on post-operative day 2-3, with 45-60 Gy delivered to a 1 cm margin. All patients underwent subsequent standard radiation/temozolomide treatment 4-5 weeks post-irradiation. There were no wound related complications. Toxicity was observed in two patients (2/11 or 18 %), including one post-operative seizure and one case of cerebral edema that resolved after a course of steroid treatment. Immediate post-operative and pre-irradiation/temozolomide magnetic resonance imaging assessment was available for 9 of the 11 patients. Two of these nine patients (22 %) developed new regions of contrast enhancement prior to irradiation/temozolomide. This compares favorably to historical data where 53 % of patient suffer such tumor progression. While there was a trend toward improved 6 month progression free survival in the brachytherapy/temozolomide/radiation treated patients, the overall survival of these patients were comparable to historical controls. This case series demonstrates the safety of immediate post-operative brachytherapy when applied prior to EBRT and temozolomide in the treatment of newly diagnosed glioblastomas.
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Antineoplásicos Alquilantes/uso terapéutico , Braquiterapia , Neoplasias Encefálicas/terapia , Quimioradioterapia Adyuvante , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Estudios de Casos y Controles , Dacarbazina/uso terapéutico , Femenino , Estudios de Seguimiento , Glioblastoma/diagnóstico , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , Tasa de Supervivencia , TemozolomidaRESUMEN
RATIONALE: Alteplase is the only approved thrombolytic agent for acute stroke. An alternative plasminogen activator, tenecteplase, has been previously shown to increase early biological effectiveness (reperfusion) resulting in early clinical recovery in acute stroke patients with target mismatch on perfusion imaging; however, phase III data are lacking. AIM AND HYPOTHESIS: In this study, we assess the efficacy and safety of tenecteplase compared to alteplase in acute stroke patients with target mismatch on perfusion imaging. METHODS AND DESIGN: Tenecteplase (0.25 mg/kg) versus alteplase (0.9 mg/kg) for Stroke Thrombolysis Evaluation (TASTE) is a multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE), controlled phase III non-inferiority trial (2 arms with 1:1 randomization) with an adaptive sample size re-estimation in patients with acute ischemic stroke meeting target mismatch criteria on perfusion imaging. SAMPLE SIZE ESTIMATES: Recruiting 728 patients (1:1 tenecteplase vs alteplase) would yield 90% power (two-sided alpha 0.05) to detect a treatment effect of 8% (26% modified Rankin scale (mRS) 0-1 in alteplase arm and 34% mRS 0-1 in tenecteplase arm), with an absolute non-inferiority margin of 3%. Following the pre-planned "promising zone" adaptive sample size re-estimation, the final sample size was set at 832 patients. STUDY OUTCOMES: The primary outcome measure is the proportion of patients with an mRS score of 0-1 at 3 months. Secondary outcomes include the categorical shift in mRS at 3 months; the proportion of patients with: mRS 0-2, 5-6, and 6; reduction of the National Institutes of Health Stroke Scale (NIHSS) by 8 or more points or reaching 0-1 at 24 h; symptomatic intracerebral hemorrhage within 36 h; and death. DISCUSSION: This pivotal trial will provide important data on the role of tenecteplase in acute ischemic stroke, and the use of imaging-based treatment decision-making for stroke thrombolysis. CLINICAL TRIAL PROTOCOL: Trial Registration: ACTRN12613000243718, EudraCT 2015-002657-36.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Tenecteplasa/uso terapéutico , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Prospectivos , Gusto , Resultado del Tratamiento , Fibrinolíticos/uso terapéutico , Terapia Trombolítica , Isquemia Encefálica/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
The basioccipital bone is an essential developmental component to the occipital bone, occipital condyles, foramen magnum, clivus, and cranial base. The basioccipital bone joins each exoccipital bone with a basiexoccipital synchondrosis and the basisphenoid/sphenoid bone with a spheno-occipital synchondrosis. The basioccipital is found intermediate to the petrous temporal bones and forms the bilateral petrooccipital/petroclival fissures otherwise known as the petrooccipital complex. Thus, the basioccipital bone is a central component to the developing cranial base. Despite the importance of basioccipital development in cranial ontogeny, there has been limited study of basioccipital ontogeny. This study assessed 98 disarticulated human basioccipital bones from a perinatal population ranging in age-at-death from 5-months intrauterine to 5-months post-natal development. Size and shape of basioccipital bones were assessed with traditional and extended eigenshape geometric morphometric analysis. The results of this study demonstrate that the basioccipital bone grows in width at a faster rate than it grows in length. The maximum basioccipital width surpassed the midsagittal length at approximately 7-months intrauterine development. Canonical variate analysis revealed statistically significant shape change occurring from a relatively narrow/elongate (anterior-to-posterior) basiocciput shape with mild concavity at the foramen magnum in the fifth and sixth intrauterine months to a relatively broad/stout basiocciput shape with more pronounced concavity in the postnatal months. Likewise, growth rate in total length was greater than midsagittal length, demonstrating enlargement of concavity in the anterior foramen magnum over time. This report provides insight into cranial development and aids in estimating age-at-death among fetuses and infants.
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Feto , Hueso Occipital , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Base del Cráneo , Hueso EsfenoidesRESUMEN
PURPOSE: This study seeks to characterize magnetic resonance imaging (MRI) changes following stereotactic radiosurgery (SRS) of pediatric brain malignancies. METHODS: Serial MRI evaluations were performed on 21 lesions treated with SRS for either medulloblastoma (n=12), juvenile pilocytic astrocytoma (n=4), ependymoma (n=2), atypical rhabdoid teratoid tumor (n=2), or pineocytoma (n=1). Prescription doses ranged from 14 to 30 Gy in one to five fractions. Tumor response was qualified as complete (CR), partial (PR), stable disease (SD), or progressive disease (PD) according to the RECIST v1.1. Median radiographic follow-up after SRS was 17 months. RESULTS: A total of 80 follow-up MRI scans were reviewed with a median of eight per patient. During serial MRI evaluation, eight lesions met criteria for PD at a median of 6 months. However, of these, three (37%) represented transient tumor edema with two lesions later developing a CR at a median of 15 months and one persisting as SD at 12 months. The remaining five lesions were true local failures. Of the 13 lesions that did not show evidence of PD, a CR was obtained in 11 lesions at a median of 3 months (range, 2-6), and SD was seen in the remaining two tumors at last follow-up. CONCLUSION: Lesion enlargement following SRS for pediatric intracranial tumors is common, and a proportion of patients meeting requirements for PD at early radiographic follow-up may later develop complete resolution of their lesions. Physicians should be aware of these radiographic changes to avoid unwarranted medical and surgical interventions.
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Neoplasias Encefálicas/cirugía , Encéfalo/cirugía , Glioma/cirugía , Radiocirugia/métodos , Adolescente , Encéfalo/patología , Neoplasias Encefálicas/patología , Niño , Preescolar , Glioma/patología , Humanos , Imagen por Resonancia Magnética , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Advance care planning (ACP) is a clinical skill that can be taught. An opportunity exists to teach how to conduct ACP to clinicians not typically engaged in these conversations to increase the likelihood that patients and caregivers engage in ACP. We conducted a prospective study exploring the feasibility of a pharmacist-led ACP intervention. METHODS: We completed a prospective, single-center study from July 2015 to July 2017. We included patients of age ≥ 18 years with incurable cancer referred to the palliative care clinic. A trained pharmacist led an ACP discussion with the patient and selected proxy. We defined feasibility as completion of ≥ 30 pharmacist-led ACP discussions over the study period. Additionally, we defined an informed healthcare proxy as someone who understood three key end-of-life (EOL) treatment preferences: the patient's personal definition of quality of life, desired resuscitation status, and preferred location of death (in or out of the hospital). Patients were followed until the end of the study or death. For those patients who died, the pharmacist contacted the proxy for follow-up and explored satisfaction with the ACP intervention. RESULTS: Thirty-four patients completed the study. All selected proxies completed the intervention and were able to understand the three EOL preferences. At the time of the patient's death (n = 20), proxies reported that 66.6% received their preferred resuscitation status and 72.2% died in their preferred location. Proxy satisfaction with the ACP process was 7.6 ± 2.5 (mean ± SD) on a 11-point Likert scale. CONCLUSION: These findings indicate the potential for pharmacists to lead and engage in ACP in the outpatient setting.
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Planificación Anticipada de Atención , Farmacéuticos , Adolescente , Directivas Anticipadas , Humanos , Estudios Prospectivos , Calidad de VidaRESUMEN
VEGF is the best characterized mediator of tumor angiogenesis. Anti-VEGF agents have recently demonstrated impressive efficacy in human cancer trials, but the optimal dosing of such agents must still be determined empirically, because biomarkers to guide dosing have yet to be established. The widely accepted (but unverified) assumption that VEGF production is quite low in normal adults led to the notion that increased systemic VEGF levels might quantitatively reflect tumor mass and angiogenic activity. We describe an approach to determine host and tumor production of VEGF, using a high-affinity and long-lived VEGF antagonist now in clinical trials, the VEGF Trap. Unlike antibody complexes that are usually rapidly cleared, the VEGF Trap forms inert complexes with tissue- and tumor-derived VEGF that remain stably in the systemic circulation, where they are readily assayable, providing unprecedented capability to accurately measure VEGF production. We report that VEGF production is surprisingly high in non-tumor-bearing rodents and humans, challenging the notion that systemic VEGF levels can serve as a sensitive surrogate for tumor load; tumor VEGF contribution becomes significant only with very large tumor loads. These findings have the important corollary that anti-VEGF therapies must be sufficiently dosed to avoid diversion by host-derived VEGF. We further show that our assay can indicate when VEGF is optimally blocked; such biomarkers to guide dosing do not exist for other anti-VEGF agents. Based on this assay, VEGF Trap doses currently being assessed in clinical trials are in the efficacious range.
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Inhibidores de la Angiogénesis/farmacología , Factores de Crecimiento Endotelial Vascular/biosíntesis , Envejecimiento/fisiología , Inhibidores de la Angiogénesis/inmunología , Animales , Anticuerpos/inmunología , Biomarcadores , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones SCID , Unión Proteica , Factores de Crecimiento Endotelial Vascular/sangre , Factores de Crecimiento Endotelial Vascular/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/patologíaRESUMEN
Burkholderia pseudomallei is a biothreat agent and an important natural pathogen, causing melioidosis in humans and animals. A type III secretion system (TTSS-3) has been shown to be critical for virulence. Because TTSS components from other pathogens have been used successfully as diagnostic agents and as experimental vaccines, it was investigated whether this was the case for BipB, BipC and BipD, components of B. pseudomallei's TTSS-3. The sequences of BipB, BipC and BipD were found to be highly conserved among B. pseudomallei and B. mallei isolates. A collection of monoclonal antibodies (mAbs) specific for each Bip protein was obtained. Most recognized both native and denatured Bip protein. Burkholderia pseudomallei or B. mallei did not express detectable BipB or BipD under the growth conditions used. However, anti-BipD mAbs did recognize the TTSS needle structures of a Shigella strain engineered to express BipD. The authors did not find that BipB, BipC or BipD are protective antigens because vaccination of mice with any single protein did not result in protection against experimental melioidosis. Enzyme-linked immunosorbent assay (ELISA) studies showed that human melioidosis patients had antibodies to BipB and BipD. However, these ELISAs had low diagnostic accuracy in endemic regions, possibly due to previous patient exposure to B. pseudomallei.
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Anticuerpos Antibacterianos , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Burkholderia pseudomallei/inmunología , Proteínas Portadoras/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Monoclonales , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Burkholderia mallei/genética , Burkholderia pseudomallei/genética , Proteínas Portadoras/genética , Secuencia Conservada , ADN Bacteriano/química , ADN Bacteriano/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Melioidosis/inmunología , Melioidosis/prevención & control , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Shigella/genética , Análisis de Supervivencia , Vacunas de Subunidad/genética , Vacunas de Subunidad/inmunologíaRESUMEN
INTRODUCTION: Group prenatal care may have benefits over traditional care; however, the economic performance of this model is largely unexplored. We sought to understand the finances of group prenatal care at a small, rural, critical access hospital. METHODS: Volume, cost, and revenue estimates were obtained and an economic model was created. Determination was made of total time spent providing prenatal care, financial breakeven point and number of hours of prenatal care per patient. RESULTS: Group size required to equal or exceed the time efficiency of traditional prenatal care varied based on the structure of the prenatal care models. Small group sizes decrease efficiency and increase costs. The baseline financial breakeven point of 305 deliveries per year decreases to 302 deliveries if all women receive group care. Shifting prenatal care from higher to lower cost providers decreases the breakeven point to 218 deliveries per year, if the acquired time is used to provide gynecologic services. With group sizes between eight and 12, the time efficiency of lower cost providers improves from an average of seven to four hours of prenatal care per patient. CONCLUSION: In organizations with low volume obstetrics, group prenatal care can lead to decreased efficiency and greater cost. In settings with sufficient volume, financial benefit is realized if prenatal care is shifted from higher to lower cost providers. Using a group model of prenatal care allows lower cost providers to see additional patients efficiently. Although group prenatal care may offer some benefits, cost analysis should be considered before initiation.
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Hospitales Rurales/organización & administración , Atención Prenatal/métodos , Mujeres , Costos y Análisis de Costo , Eficiencia Organizacional , Femenino , Humanos , Modelos Económicos , Embarazo , Factores de TiempoRESUMEN
BACKGROUND: Students living in rural areas of the United States exhibit lower levels of educational attainment than their suburban counterparts. Innovative interventions are needed to close this educational achievement gap. AIMS: We investigated whether an online growth mindset intervention could be leveraged to promote academic outcomes. SAMPLE: We tested the mindset intervention in a sample of 222 10th-grade adolescent girls (M age = 15.2; 38% White, 25% Black, 29% Hispanic) from four rural, low-income high schools in the Southeastern United States. METHODS: We conducted a randomized controlled trial to test the efficacy of the growth mindset intervention, relative to a sexual health programme. We used random sampling and allocation procedures to assign girls to either the mindset intervention (n = 115) or an attention-matched control programme (n = 107). We assessed participants at pre-test, immediate post-test, and 4-month follow-up. RESULTS: Relative to the control condition, students assigned to the mindset intervention reported stronger growth mindsets at immediate post-test and 4-month follow-up. Although the intervention did not have a total effect on academic attitudes or grades, it indirectly increased motivation to learn, learning efficacy and grades via the shifts in growth mindsets. CONCLUSIONS: Results indicate that this intervention is a promising method to encourage growth mindsets in rural adolescent girls.
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Éxito Académico , Inteligencia , Aprendizaje , Psicoterapia/métodos , Autoeficacia , Autocontrol , Conducta Sexual , Habilidades Sociales , Adolescente , Femenino , Estudios de Seguimiento , Humanos , Pobreza , Población Rural , Autocontrol/psicología , Conducta Sexual/psicología , Sudeste de Estados Unidos , Resultado del TratamientoRESUMEN
OBJECTIVE: To review effective approaches for non-pain symptom management for cancer patients focusing on treatment of nausea and vomiting, constipation, diarrhea, anorexia/cachexia, fatigue, and dyspnea. DATA SOURCES: Peer-reviewed articles, clinical practice guidelines, professional organization position statements. CONCLUSION: Oncology nurses are key advocates for optimal symptom management. Maximizing palliation of symptoms improves quality of life and prolongs survival. IMPLICATIONS FOR NURSING PRACTICE: To provide an evidence-based approach to symptom management, oncology nurses require a deep understanding of symptom pathophysiology while anticipating side effects, educating patients and caregivers, considering psychosocial/spiritual factors, exploring treatment expectations, and clarifying goals of treatment.
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Enfermería de Cuidados Paliativos al Final de la Vida/organización & administración , Neoplasias/enfermería , Rol de la Enfermera , Enfermería Oncológica/organización & administración , Manejo del Dolor/enfermería , Cuidados Paliativos/organización & administración , Atención Integral de Salud/organización & administración , Humanos , Relaciones Enfermero-Paciente , Calidad de la Atención de SaludRESUMEN
Screening, diagnosis, and treatment of gestational diabetes mellitus (GDM) are common practice, despite controversy regarding benefits. A review of the literature from 1950 to 2006 revealed 3 randomized controlled trials evaluated the treatment of GDM but 2 of these studies lacked power to detect a difference in outcomes. The single trial with sufficient power showed a 67% lower rate of serious perinatal complication (a composite of shoulder dystocia, nerve injury, fracture, and death) and a 53% lower rate of macrosomia with treatment of GDM. There are no well-designed studies evaluating screening or diagnostic strategies. Treatment of GDM may improve some neonatal and obstetric outcomes, but there is limited evidence useful for determining the best screening method or diagnostic test, strategy, and criteria. Ongoing studies may provide some evidence to guide future research and clinical practice.
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Diabetes Gestacional/diagnóstico , Tamizaje Masivo/métodos , Complicaciones del Embarazo/diagnóstico , Resultado del Embarazo , Femenino , Macrosomía Fetal/epidemiología , Macrosomía Fetal/prevención & control , Humanos , Embarazo , Medición de RiesgoRESUMEN
With the continued expansion of electronic patient record systems ahead of comprehensive evidence, metrics, or future-proofing, health informatics in Europe and beyond is embarking on a faith-driven adventure that also risks data swamping of end-users. An alternative approach is an information broker system, drawing from departmental data sources. A 3-year study in health and social care has produced a first demonstrator which can search for specified information in heterogeneous distributed data stores, with source-specific permission can copy it, and then merge the search results into one integrated picture in a real-time process which is also captured in an audit system. The research project has addressed a number of issues during the study, including updating the concepts of role-based access, semantic interoperability, and harnessing web-based services bound at the time of need. A demonstrator now exists, and provides a platform for further application and development research. This paper summarises how this opens up a viable alternative approach for the next generation of health record systems, enabling record searching and integration as and when it is needed for specific patient-related purposes, whilst being independent of organisations, diagnostic approaches, or service delivery structures, and reducing the risks of data swamping.