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1.
Angew Chem Int Ed Engl ; 63(23): e202401368, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38584127

RESUMEN

Polaritonic chemistry is emerging as a powerful approach to modifying the properties and reactivity of molecules and materials. However, probing how the electronics and dynamics of molecular systems change under strong coupling has been challenging due to the narrow range of spectroscopic techniques that can be applied in situ. Here we develop microfluidic optical cavities for vibrational strong coupling (VSC) that are compatible with nuclear magnetic resonance (NMR) spectroscopy using standard liquid NMR tubes. VSC is shown to influence the equilibrium between two conformations of a molecular balance sensitive to London dispersion forces, revealing an apparent change in the equilibrium constant under VSC. In all compounds studied, VSC does not induce detectable changes in chemical shifts, J-couplings, or spin-lattice relaxation times. This unexpected finding indicates that VSC does not substantially affect molecular electron density distributions, and in turn has profound implications for the possible mechanisms at play in polaritonic chemistry under VSC and suggests that the emergence of collective behavior is critical.

2.
ESMO Open ; 9(3): 102945, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38471240

RESUMEN

BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS mutations are often associated with poorer survival; however, the prognostic impact of specific point mutations is unclear. In the phase III SUNLIGHT trial, trifluridine/tipiracil (FTD/TPI) plus bevacizumab significantly improved overall survival (OS) versus FTD/TPI alone. We assessed the impact of KRASG12 mutational status on OS in SUNLIGHT. PATIENTS AND METHODS: In the global, open-label, randomized, phase III SUNLIGHT trial, adults with mCRC who had received no more than two prior chemotherapy regimens were randomized 1 : 1 to receive FTD/TPI alone or FTD/TPI plus bevacizumab. In this post hoc analysis, OS was assessed according to the presence or absence of a KRASG12 mutation in the overall population and in patients with RAS-mutated tumors. RESULTS: Overall, 450 patients were analyzed, including 302 patients in the RAS mutation subgroup (214 with a KRASG12 mutation and 88 with a non-KRASG12RAS mutation). In the overall population, similar OS outcomes were observed in patients with and without a KRASG12 mutation [median 8.3 and 9.2 months, respectively; hazard ratio (HR) 1.09, 95% confidence interval (CI) 0.87-1.4]. Similar OS outcomes were also observed in the subgroup analysis of patients with a KRASG12 mutation versus those with a non-KRASG12RAS mutation (HR 1.03, 95% CI 0.76-1.4). FTD/TPI plus bevacizumab improved OS compared with FTD/TPI alone irrespective of KRASG12 mutational status. Among patients with a KRASG12 mutation, the median OS was 9.4 months with FTD/TPI plus bevacizumab versus 7.2 months with FTD/TPI alone (HR 0.67, 95% CI 0.48-0.93), and in patients without a KRASG12 mutation, the median OS was 11.3 versus 7.1 months, respectively (HR 0.59, 95% CI 0.43-0.81). CONCLUSIONS: The presence of a KRASG12 mutation had no detrimental effect on OS among patients treated in SUNLIGHT. The benefit of FTD/TPI plus bevacizumab over FTD/TPI alone was confirmed independently of KRASG12 status.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Pirrolidinas , Timina , Adulto , Humanos , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Uracilo/uso terapéutico , Trifluridina/efectos adversos , Demencia Frontotemporal/inducido químicamente , Neoplasias del Colon/tratamiento farmacológico , Mutación
3.
Am J Phys Med Rehabil ; 102(3): 275-283, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36730285

RESUMEN

ABSTRACT: Increasing medical student exposure to physical medicine and rehabilitation is an important factor for future growth of the field. Therefore, it is important to determine which types of interventions during medical school have the greatest impact on medical students' decision to pursue a career in physical medicine and rehabilitation. The purpose of this study is to perform a scoping review of the current literature that has analyzed how different interventions and experiences impact medical school students' decision to pursue a career in physical medicine and rehabilitation. A systematic and comprehensive search strategy was implemented across five different journal databases and yielded 18 articles meeting the inclusion criteria. Most studies analyzing specific interventions looked only at presurvey and postsurvey comparisons of the immediate impact of the intervention on interest in physical medicine and rehabilitation, and few looked at longitudinal outcomes, such as match characteristics. The most frequently cited factor that was shown to positively impact interest in physical medicine and rehabilitation was early exposure. Participating in clinical rotations also had a positive impact but was most effective when combined with early exposure. This review highlights the need for national recommendations for integrating physical medicine and rehabilitation into all 4 yrs of medical education.


Asunto(s)
Educación Médica , Medicina , Medicina Física y Rehabilitación , Estudiantes de Medicina , Humanos , Selección de Profesión
4.
Am J Phys Med Rehabil ; 102(1): 71-74, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36228184

RESUMEN

ABSTRACT: Opportunities for early medical student exposure to the field of physical medicine and rehabilitation (PM&R) are desirable for promoting the field as a career choice and are useful for introducing students to the care of people with disabilities. The COVID-19 pandemic disrupted medical education and caused the cancellation of many in-person clinical programs, including the Medical Student Summer Clinical Externship in PM&R supported by the Association of Academic Physiatrists. This article describes the process by which an in-person summer clinical externship program was effectively converted into a Virtual PM&R Experience using a combination of independent assignments and small-group sessions. A total of 87 medical students completed the Virtual PM&R Experience over two summers. The participants of the program met the program learning objectives, including enhancing their understanding of physiatry as a career and recognizing the medical and social issues that affect persons with disability.


Asunto(s)
COVID-19 , Medicina Física y Rehabilitación , Estudiantes de Medicina , Humanos , Pandemias , Selección de Profesión
5.
ESMO Open ; 7(6): 100633, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36455504

RESUMEN

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) showed clinical benefit, including improved survival and manageable safety in previously treated patients with metastatic colorectal (mCRC) or gastric/gastroesophageal junction (mGC/GEJC) cancer in the phase III RECOURSE and TAGS trials, respectively. A pooled analysis was conducted to further characterize FTD/TPI safety, including management of haematologic toxicities and use in patients with renal or hepatic impairment. PATIENTS AND METHODS: Adults with ≥2 prior regimens for advanced mGC/GEJC or mCRC were randomized (2 : 1) to FTD/TPI [35 mg/m2 twice daily days 1-5 and 8-12 (28-day cycle); same dosage in both trials] or placebo plus best supportive care. Adverse events (AEs) were summarized in the safety population (patients who received ≥1 dose) and analysed by renal/hepatic function. RESULTS: TAGS and RECOURSE included 335 and 533 FTD/TPI-treated and 168 and 265 placebo-treated patients, respectively. Overall safety of FTD/TPI was similar in TAGS and RECOURSE. Haematologic (neutropenia, anaemia) and gastrointestinal (nausea, diarrhoea) AEs were most commonly observed. Laboratory-assessed grade 3-4 neutropenia occurred in 37% (TAGS)/38% (RECOURSE) of FTD/TPI-treated patients (median onset: 29 days/55 days), and 96% (TAGS)/97% (RECOURSE) of cases resolved regardless of renal/hepatic function. Supportive medications for neutropenia were received by 17% (TAGS) and 9% (RECOURSE); febrile neutropenia was reported in 2% and 4%, respectively. Overall grade ≥3 AEs were more frequent in patients with moderate renal impairment [81% (TAGS); 85% (RECOURSE)] versus normal renal function (74%; 67%); anaemia and neutropenia were more common in patients with renal impairment. FTD/TPI safety (including haematologic AEs) was consistent across patients with normal and mildly impaired hepatic function. CONCLUSIONS: These results support FTD/TPI as a well-tolerated treatment in patients with mGC/GEJC or mCRC, with a consistent safety profile. Safety was largely similar in patients with normal or mildly impaired renal/hepatic function; however, patients with renal impairment should be monitored for haematologic toxicities.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Neutropenia , Neoplasias Gástricas , Adulto , Humanos , Trifluridina/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Demencia Frontotemporal/inducido químicamente , Uracilo/efectos adversos , Timina/efectos adversos , Pirrolidinas/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Unión Esofagogástrica/patología , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico
8.
ESMO Open ; 7(3): 100511, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35688062

RESUMEN

BACKGROUND: KRAS gene mutations can predict prognosis and treatment response in patients with metastatic colorectal cancer (mCRC). METHODS: We undertook a meta-analysis of three randomized, placebo-controlled trials (RECOURSE, TERRA and J003) to investigate the impact of KRAS mutations in codons 12 or 13 on overall survival (OS) and progression-free survival in patients receiving trifluridine/tipiracil (FTD/TPI) for refractory mCRC. RESULTS: A total of 1375 patients were included, of whom 478 had a KRAS codon 12 mutation and 130 had a KRAS codon 13 mutation. In univariate analyses, the absence of a KRAS codon 12 mutation was found to significantly increase the OS benefit of FTD/TPI relative to placebo compared with the presence of the mutation {hazard ratio (HR), 0.62 [95% confidence interval (CI): 0.53-0.72] versus 0.86 (0.70-1.05), respectively; interaction P = 0.0206}. Multivariate analyses showed that taking confounding factors into account reduced the difference in treatment effect between the presence and the absence of KRAS codon 12 mutations, confirming that treatment benefit was maintained in patients with [HR, 0.73 (95% CI: 0.59-0.89)] and without [HR, 0.63 (95% CI: 0.54-0.74)] codon 12 mutations (interaction P = 0.2939). KRAS mutations in codon 13 did not reduce the OS benefit of FTD/TPI relative to placebo, and, furthermore, KRAS mutations at either codon 12 or codon 13 did not affect the progression-free survival benefit. CONCLUSIONS: Treatment with FTD/TPI produced a survival benefit, relative to placebo, regardless of KRAS codon 12 or 13 mutation status in patients with previously treated mCRC.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Codón/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Demencia Frontotemporal/inducido químicamente , Demencia Frontotemporal/tratamiento farmacológico , Demencia Frontotemporal/genética , Humanos , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Pirrolidinas , Ensayos Clínicos Controlados Aleatorios como Asunto , Timina , Trifluridina/farmacología , Trifluridina/uso terapéutico , Uracilo/uso terapéutico
9.
JACC Clin Electrophysiol ; 8(6): 754-762, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35738852

RESUMEN

BACKGROUND: The RAID (Ranolazine Implantable Cardioverter-Defibrillator) randomized placebo-controlled trial showed that ranolazine treatment was associated with reduction in recurrent ventricular tachycardia (VT) requiring appropriate implantable cardioverter-defibrillator (ICD) therapy. OBJECTIVES: This study aimed to identify groups of patients in whom ranolazine treatment would result in the highest reduction of ventricular tachyarrhythmia (VTA) burden. METHODS: Andersen-Gill analyses were performed to identify variables associated with risk for VTA burden among 1,012 patients enrolled in RAID. The primary endpoint was VTA burden defined as VTA episodes requiring appropriate treatment. RESULTS: Multivariate analysis identified 7 factors associated with increased VTA burden: history of VTA, age ≥65 years, New York Heart Association functional class ≥III, QRS complex (≥130 ms), low ejection fraction (<30%), atrial fibrillation (AF), and concomitant antiarrhythmic drug (AAD) therapy. The effect of ranolazine on VTA burden was seen among patients without concomitant AAD therapy (HR [HR]: 0.68; 95% CI: 0.55-0.84; P < 0.001), whereas no effect was seen among those who are concomitantly treated with other AADs (HR: 1.33; 95% CI: 0.90-1.96; P = 0.16); P = 0.003 for interaction. In patients with cardiac resynchronization therapy (CRT) ICDs, ranolazine treatment was associated with a 36% risk reduction for VTA recurrence (HR: 0.64; 95% CI: 0.47-0.86; P < 0.001), whereas among patients with ICDs without CRT no significant effect was noted (HR: 0.94; 95% CI: 0.74-1.18; P = 0.57); P = 0.047 for interaction. CONCLUSIONS: In patients with high risk for VTA, ranolazine is effective in reducing VTA burden, with significantly greater effect in CRT-treated patients, those without AF, and those not treated with concomitant AADs. In patients already on AADs or those with AF, the addition of ranolazine did not affect VTA burden. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).


Asunto(s)
Desfibriladores Implantables , Ranolazina , Taquicardia Ventricular , Anciano , Humanos , Ranolazina/uso terapéutico , Taquicardia Ventricular/prevención & control
10.
Am J Phys Med Rehabil ; 101(7): 693-697, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35034055

RESUMEN

ABSTRACT: The Medical Student Summer Clinical Externship is an 8-wk program hosted by the Association of Academic Physiatrists and offered to first year medical students. Various institutions sponsor participants and provide clinical exposure and mentorship opportunities to promote interest in the field. The program has had more than 100 medical student participants. Students were asked to complete a preparticipation and postparticipation survey. Results revealed a statistically significant increase in interest in physiatry and participants' scores for comfort and experience level in obtaining a history of present illness, general physical examination, and managing developmental, musculoskeletal, and neurologic disabilities. The Medical Student Summer Clinical Externship program provides an opportunity for mentorship and exposure to various subspecialties that likely reinforces student interest in those who are predisposed to physiatry. Students' increased comfort level in treating patients with developmental, musculoskeletal, and neurologic disabilities may lead to improvements in the quality of and access to care received by these populations. All participants gain an increased awareness of the scope of practice of physiatry that will hopefully lead to the increased integration of physical medicine and rehabilitation into the care plans and as a standard of care for patients who might greatly benefit.


Asunto(s)
Fisiatras , Medicina Física y Rehabilitación , Estudiantes de Medicina , Humanos , Examen Físico , Encuestas y Cuestionarios
11.
AIDS Behav ; 26(2): 613-622, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34355286

RESUMEN

The CD4 depletion model estimates diagnosis delays by approximating infection date from CD4 T-cell count at diagnosis, and back-calculation can compute the proportion of undiagnosed PLWHA. The model assumes the immigration of PLWHA to the U.S. is negligible and counts as a transmission event, which may be impractical outside high prevalence states. Duration of U.S. residency among foreign-born PLWHA and diagnosis delays were compared. The impact on estimates of undiagnosed PLWHA was tested through simulation with different proportions of foreign-born people assumed to have acquired HIV abroad. In 67% of foreign-born people, the mean (SD) years of delay (9.9 (6.3)) exceeded the duration of U.S. residency (2.0 (1.9)). Additionally, inaccuracies in the estimates for proportions of undiagnosed PLWHA were pronounced when foreign-born people who acquired HIV abroad comprised 30% of diagnoses. The CD4 model inadvertently misclassified some diagnoses as in-state transmission events. Consequently, simulated results demonstrated inaccuracies and unstable calculations.


Asunto(s)
Infecciones por VIH , Recuento de Linfocito CD4 , Emigración e Inmigración , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Incidencia , Prevalencia
12.
Circ Res ; 127(4): 502-518, 2020 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-32366200

RESUMEN

RATIONALE: The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive a proteasome inhibitor-containing regime show cardiotoxicity. Moreover, UPS and autophagic-lysosomal pathway defects are implicated in cardiac pathogenesis. Hence, a better understanding of the cross-talk between the 2 catabolic pathways will help advance cardiac pathophysiology and medicine. OBJECTIVE: Systemic proteasome inhibition (PSMI) was shown to increase p62/SQSTM1 expression and induce myocardial macroautophagy. Here we investigate how proteasome malfunction activates cardiac autophagic-lysosomal pathway. METHODS AND RESULTS: Myocardial macroautophagy, TFEB (transcription factor EB) expression and activity, and p62 expression were markedly increased in mice with either cardiomyocyte-restricted ablation of Psmc1 (an essential proteasome subunit gene) or pharmacological PSMI. In cultured cardiomyocytes, PSMI-induced increases in TFEB activation and p62 expression were blunted by pharmacological and genetic calcineurin inhibition and by siRNA-mediated Molcn1 silencing. PSMI induced remarkable increases in myocardial autophagic flux in wild type mice but not p62 null (p62-KO) mice. Bortezomib-induced left ventricular wall thickening and diastolic malfunction was exacerbated by p62 deficiency. In cultured cardiomyocytes from wild type mice but not p62-KO mice, PSMI induced increases in LC3-II flux and the lysosomal removal of ubiquitinated proteins. Myocardial TFEB activation by PSMI as reflected by TFEB nuclear localization and target gene expression was strikingly less in p62-KO mice compared with wild type mice. CONCLUSIONS: (1) The activation of cardiac macroautophagy by proteasomal malfunction is mediated by the Mocln1-calcineurin-TFEB-p62 pathway; (2) p62 unexpectedly exerts a feed-forward effect on TFEB activation by proteasome malfunction; and (3) targeting the Mcoln1 (mucolipin1)-calcineurin-TFEB-p62 pathway may provide new means to intervene cardiac autophagic-lysosomal pathway activation during proteasome malfunction.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Calcineurina/metabolismo , Macroautofagia/fisiología , Complejo de la Endopetidasa Proteasomal/fisiología , ATPasas Asociadas con Actividades Celulares Diversas/genética , Animales , Antineoplásicos/farmacología , Bortezomib/farmacología , Calcineurina/genética , Inhibidores de la Calcineurina , Hipertrofia Ventricular Izquierda/inducido químicamente , Lisosomas/metabolismo , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Inhibidores de Proteasoma , Proteostasis , ARN Interferente Pequeño , Ratas , Proteína Sequestosoma-1/metabolismo , Transducción de Señal/fisiología , Canales de Potencial de Receptor Transitorio/metabolismo , Ubiquitina/metabolismo , Regulación hacia Arriba
13.
Ann Oncol ; 31(1): 88-95, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31912801

RESUMEN

BACKGROUND: The phase II J003 (N = 169) and phase III RECOURSE (N = 800) trials demonstrated a significant improvement in survival with trifluridine (FTD)/tipiracil (TPI) versus placebo in patients with refractory metastatic colorectal cancer. This post hoc analysis investigated pharmacokinetic data of FTD/TPI exposure and pharmacodynamic markers, such as chemotherapy-induced neutropenia (CIN) and clinical outcomes. PATIENTS AND METHODS: A total of 210 patients from RECOURSE were enrolled in this substudy. A limited sampling approach was used, with three pharmacokinetic samples drawn on day 12 of cycle 1. Patients were categorized as being above or below the median area under the plasma concentration-time curve (AUC) for FTD and TPI. We conducted a post hoc analysis using the entire RECOURSE population to determine the correlations between CIN and clinical outcome. We then carried out a similar analysis on the J003 trial to validate the results. RESULTS: In the RECOURSE subset, patients in the high FTD AUC group had a significantly increased CIN risk. Analyses of the entire population demonstrated that FTD/TPI-treated patients with CIN of any grade in cycles 1 and 2 had significantly longer median overall survival (OS) and progression-free survival (PFS) than patients who did not develop CIN and patients in the placebo group. Patients who required an FTD/TPI treatment delay had increased OS and PFS versus those in the placebo group and those who did not develop CIN. Similar results were obtained in the J003 cohort. CONCLUSIONS: In RECOURSE, patients with higher FTD drug exposure had an increased CIN risk. FTD/TPI-treated patients who developed CIN had improved OS and PFS versus those in the placebo group and those who did not develop CIN. Similar findings were reported in the J003 cohort, thus validating the RECOURSE results. The occurrence of CIN may be a useful predictor of treatment outcomes for FTD/TPI-treated patients. CLINICALTRIALS. GOV IDENTIFIER: NCT01607957 (RECOURSE). JAPAN PHARMACEUTICAL INFORMATION CENTER NUMBER: JapicCTI-090880 (J003).


Asunto(s)
Neoplasias Colorrectales , Neutropenia , Neoplasias Colorrectales/tratamiento farmacológico , Combinación de Medicamentos , Humanos , Japón , Pirrolidinas , Timina , Trifluridina/efectos adversos , Uracilo/efectos adversos
14.
Khirurgiia (Mosk) ; (11): 5-12, 2019.
Artículo en Inglés, Ruso | MEDLINE | ID: mdl-31714523

RESUMEN

OBJECTIVE: To analyze early and delayed results of various variants of circular tracheal resection (CTR) with anastomosis, to determine the safest approach, dates and conditions of correction, features of postoperative period in patients after previous tracheal surgery. MATERIAL AND METHODS: There were 831 patients with cicatricial tracheal stenosis. CTR was made in 330 (39.7%) patients. Most patients had previous prolonged ICU-stay. The patients were divided into 4 groups. Group 1 consisted of 61 (18.5%) patients after previous prolonged tracheal stenting. Group 2 included 45 (13.6%) patients who underwent circular tracheal resection with a functioning tracheostomy. Tracheostomy tube served as a stent in these patients. Group 3 enrolled 32 (9.7%) patients with previous staged reconstructive plastic surgeries on cranial segment of the respiratory tract. Tracheostomy or stent were absent in 192 (58.2%) patients who underwent circular tracheal resection at the first hospitalization. These patients were enrolled into the fourth (control) group. Favorable outcomes (without complications and mortality) were achieved in 85.5% (n=282) of patients. Postoperative complications occurred in 48 (14.5%) patients. Mortality rate was 0.6% (n=2). The greatest number of complications including anastomositis and restenosis was noted in patients after CTR and previous tracheoplasty with T-tube (n=8, 25%). The most common complication in patients after tracheal resection and previous stenting was anastomositis (14.7%). Long-term results depended on postoperative complications and methods of their correction. Recurrent stenosis occurred in 5 (1.5%) patients within the period of 3 months - 8 years. CTR after previous tracheoplasty with T-tube was carried out in 4 of these patients. CONCLUSION: Tracheal resection after preliminary stenting or tracheostomy is quite safe and technically feasible. Stenting allows postponing radical surgery for correction of concomitant diseases and closure of tracheostomy as a focus of infection within the surgical approach and further tracheal anastomosis. Tracheal resection with simultaneous closure of tracheostomy results a higher rate of postoperative complications compared with preliminary stenting.


Asunto(s)
Constricción Patológica/cirugía , Stents/efectos adversos , Estenosis Traqueal/cirugía , Traqueostomía/efectos adversos , Constricción Patológica/etiología , Humanos , Estudios Retrospectivos , Tráquea/patología , Tráquea/cirugía , Estenosis Traqueal/etiología
15.
Acad Med ; 94(6): 781-788, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30844926

RESUMEN

People with disabilities constitute 22.2% of the population in the United States, and virtually all physicians have people with disabilities in their clinical practice across a wide range of diagnostic groups. However, studies demonstrate that people with disabilities are inadequately served by the health care system, leading to high costs and poor outcomes. The authors argue that one cause of this discrepancy is that medical students receive limited training in the care of people with disabilities and may therefore not be able to adequately meet the competencies that underlie the Core Entrustable Professional Activities for Entering Residency. To address these gaps, the authors present practical examples of integrating concepts of disability into the curriculum with minimal additional time requirements. A comprehensive disability curriculum is suggested to include active classroom learning, clinical, and community-based experiences. At institutions that do not have a comprehensive curriculum, the authors recommend adding disability-related knowledge and skill acquisition to existing curricula through modifications to current case-based learning, simulated patients, and objective structured clinical examinations. To facilitate curriculum development, they recommend that the World Health Organization International Classification of Functioning, Disability, and Health be used as a tool to build disability concepts into active learning. The goal of these recommended curricular changes is to enhance student performance in the clinical management of people with disabilities and to better train all future physicians in the care of this population.


Asunto(s)
Competencia Clínica/normas , Curriculum/normas , Atención a la Salud/economía , Personas con Discapacidad/psicología , Competencia Clínica/estadística & datos numéricos , Atención a la Salud/normas , Educación Médica/métodos , Humanos , Internado y Residencia/métodos , Médicos/estadística & datos numéricos , Aprendizaje Basado en Problemas/métodos , Estudiantes de Medicina , Estados Unidos/epidemiología , Organización Mundial de la Salud/organización & administración
16.
Animal ; 13(1): 119-126, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29669613

RESUMEN

Rib bone biopsy samples are often used to estimate changes in skeletal mineral reserves in cattle but differences in sampling procedures and the bone measurements reported often make interpretation and comparisons among experiments difficult. 'Full-core' rib bone biopsy samples, which included the external cortical bone, internal cortical bone and trabecular bone (CBext, CBint and Trab, respectively), were obtained from cattle known to be in phosphorus (P) adequate (Padeq) or severely P-deficient (Pdefic) status. Experiments 1 and 2 examined growing steers and Experiment 3 mature breeder cows. The thickness of cortical bone, specific gravity (SG), and the amount and concentration of ash and P per unit fresh bone volume, differed among CBext, CBint and Trab bone. P concentration (mg/cc) was closely correlated with both SG and ash concentrations (pooled data, r=0.99). Thickness of external cortical bone (CBText) was correlated with full-core P concentration (FC-Pconc) (pooled data, r=0.87). However, an index, the amount of P in CBext per unit surface area of CBext (PSACB; mg P/mm2), was more closely correlated with the FC-Pconc (pooled data, FC-Pconc=37.0+146×PSACB; n=42, r=0.94, RSD=7.7). Results for measured or estimated FC-Pconc in 10 published studies with cattle in various physiological states and expected to be Padeq or in various degrees of Pdefic status were collated and the ranges of FC-Pconc indicative of P adequacy and P deficiency for various classes of cattle were evaluated. FC-Pconc was generally in the range 130 to 170 and 100 to 120 mg/cc fresh bone in Padeq mature cows and young growing cattle, respectively. In conclusion, the FC-Pconc could be estimated accurately from biopsy samples of CBext. This allows comparisons between studies where full-core or only CBext biopsy samples of rib bone have been obtained to estimate changes in the skeletal P status of cattle and facilitates evaluation of the P status of cattle.


Asunto(s)
Biopsia/veterinaria , Densidad Ósea , Bovinos/fisiología , Minerales/análisis , Costillas/química , Animales , Biopsia/métodos , Femenino , Masculino
17.
Cancer Radiother ; 22(8): 802-809, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30327228

RESUMEN

PURPOSE: The Union of Light Ion Centers in Europe (ULICE) program addressed the need for uniting scientific results for carbon-ion radiation therapy obtained by several institutions worldwide in different fields of excellence, and translating them into a real benefit to the community. Particularly, the concepts for dose/volume parameters developed in photon radiotherapy cannot be extrapolated to high linear energy transfer particles. METHODS AND MATERIALS: The ULICE-WP2 taskforce included radiation oncologists involved in carbon-ion radiation therapy and International Commission on Radiation Units and Measurements, radiation biologists, expert physicists in the fields of carbon-ion radiation therapy, microdosimetry, biological modeling and image-guided radiotherapy. Consensual reports emerged from multiple discussions within both the restricted group and the wider ULICE community. Public deliverables were produced and disseminated to the European Commission. RESULTS: Here we highlight the disparity in practices between treating centers, then address the main topics to finally elaborate specific recommendations. Although it appears relatively simple to add geometrical margins around the clinical target volume to obtain the planning target volume as performed in photon radiotherapy, this procedure is not appropriate for carbon-ion radiation therapy. Due to the variation of the radiation quality in depth, there is no generic relative biological effectiveness value for carbon-ions outside of an isolated point, for a given fractionation and specific experimental conditions. Absorbed dose and "equieffective dose" for specified conditions must always be reported. CONCLUSIONS: This work contributed to the development of standard operating procedures for carbon-ion radiation therapy clinical trials. These procedures are now being applied, particularly in the first phase III international, multicenter trial (PHRC Étoile).


Asunto(s)
Radioterapia de Iones Pesados , Instituciones Oncológicas , Consenso , Relación Dosis-Respuesta en la Radiación , Grupos Focales , Predicción , Tomografía Computarizada Cuatridimensional , Alemania , Radioterapia de Iones Pesados/métodos , Humanos , Agencias Internacionales , Japón , Tamaño de los Órganos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Oncología por Radiación/organización & administración , Oncología por Radiación/estadística & datos numéricos , Radiometría/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Efectividad Biológica Relativa , Terminología como Asunto , Carga Tumoral
19.
Epidemiol Infect ; 146(7): 920-930, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29636119

RESUMEN

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.


Asunto(s)
Coinfección/epidemiología , Infecciones por VIH/epidemiología , Hepatitis Viral Humana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Coinfección/virología , Femenino , Infecciones por VIH/virología , Hepatitis Viral Humana/virología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Salud Pública , Estados Unidos/epidemiología , Adulto Joven
20.
Rev Med Brux ; 38(3): 186-187, 2017.
Artículo en Francés | MEDLINE | ID: mdl-28653525
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