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1.
Clin Anat ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39325531

RESUMEN

Our aim was to investigate the current use of ultrasound (US) in anatomy teaching across the UK, and to discover potential obstacles in its implementation in the undergraduate medical curriculum. An electronic survey consisting of 31 questions was distributed to anatomy course organizers at all 42 UK medical schools from June to October 2022. Both quantitative and qualitative data were obtained. Analysis of quantitative data was performed using frequency tables while responses to open-ended questions were analyzed individually by authors, and themes were extracted for presentation. There was a 100% response rate, with 23 (55%) medical schools using US in anatomy teaching. Of these, 17 (74%) schools taught normal US anatomy only, while 6 (26%) included pathology. Only 3 (13%) schools delivered weekly sessions, while 3 (13%) schools delivered monthly sessions and 17 (74%) held less frequent sessions. Of the 17 schools with hands-on sessions, these were delivered by radiologists in 6 schools, while sessions in other schools were facilitated by sonographers, other clinicians, students, and anatomy department staff. Students were able to operate US machines themselves in all 17 schools delivering hands-on teaching. Limitations in resources and trained staff as well as time constraints were cited as barriers for the introduction of US in anatomy teaching. Our results indicate that only just over half of all UK medical schools use US in anatomy teaching. As US is increasingly used in screening and diagnosis by various clinicians, learning how to use US early in the medical course would be beneficial. Identifying the barriers to introducing US in the anatomical curriculum is the first step towards the successful development of an US teaching programme.

2.
World J Urol ; 42(1): 82, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358545

RESUMEN

INTRODUCTION: Prostate mpMRI was introduced in 2011 as a secondary test and subsequently integrated into a prostate cancer (PCa) diagnostics unit representing a population of approximately 550,000 people. The following represents an audit of its step-wise introduction between 2 index years, 2009 and 2018, focusing on the activity, patient outcomes and economic benefits. PATIENTS AND METHODS: The 2 distinct years were selected for relying on a transrectal ultrasound biopsy pathway in 2009 to an mpMRI-based pathway in 2018. All referrals were retrospectively screened and compared for age, PSA levels, DRE findings, biopsy history, biopsy and mpMRI allocation data. Cost analysis was determined using local unit procedure costs. RESULTS: Patients referred included 648 in 2009 and 714 in 2018. mpMRI seldomly informed decision to biopsy in 2009 (9.8%), while in 2018 it was performed in the pre-biopsy setting in 87.9% cases and enabled biopsy avoidance in 137 patients. In 2018, there was a 31.8% decrease in the number of biopsies in patients without previous PCa diagnosis, coupled with an increase in diagnostic rates of csPCa, from 28.6 to 49.0% (p < 0.0001) and a reduction in negative biopsy rates from 52.3 to 33.8%. mpMRI had a positive impact on the system with reduced patient morbidity and post-procedural complications. The estimated overall cost savings amount to approximately £75,000/year for PCa diagnosis and £11,000/year due to reduced complications. CONCLUSION: Our evaluation shows the mpMRI-based pathway has improved early detection of csPCa and reduction of repeat biopsies, resulting in significant financial benefits for the local healthcare system.


Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Imagen por Resonancia Magnética , Biopsia
3.
Small ; 20(16): e2308677, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38009515

RESUMEN

Fuel cells offer great promise for portable electricity generation, but their use is currently limited by their low durability, excessive operating temperatures, and expensive precious metal electrodes. It is therefore essential to develop fuel cell systems that can perform effectively using more robust electrolyte materials, at reasonable temperatures, with lower-cost electrodes. Recently, proton exchange membrane fuel cells have attracted attention due to their generally favorable chemical stability and quick start-up times. However, in most membrane materials, water is required for proton conduction, severely limiting operational temperatures. Here, for the first time it is demonstrated that when acidified, PAF-1 can conduct protons at high temperatures, via a unique framework diffusion mechanism. It shows that this acidified PAF-1 material can be pressed into pellets with high proton conduction properties even at high temperatures and pellet thickness, highlighting the processibility, and ease of use of this material. Furthermore, a fuel cell is shown with high power density output is possible using a non-precious metal copper electrode. Acid-doped PAF-1 therefore represents a significant step forward in the potential for a broad-purpose fuel cell due to it being cheap, robust, efficient, and easily processible.

4.
J Endourol ; 37(10): 1088-1104, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37597197

RESUMEN

Background: Numerous continence-sparing radical prostatectomy techniques have been developed to enhance postoperative early continence (EC) recovery; however, evidence regarding the best approach remains controversial. The objectives are to provide a critical appraisal of various prostatectomy techniques, based on the evidence of quality-assessed randomized control trials (RCTs); to summarize the immediate continence and the EC reported; and to propose a new standardization for continence outcomes reporting. Methods: Data acquired from five medical registries were reported to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Evidence from published, English, full-text RCTs reporting postoperative urinary continence outcomes within 6 months from surgery was included. The heterogeneity of surgical techniques and continence definitions did not allow a meta-analysis. All RCTs were critically appraised, and quality assessed. Results: In total, 39 RCTs were included: 19 of 39 studies were low-quality RCTs, presenting small cohort, monocentric, or single-surgeon data. The best RCT-supported evidence is in favor of robot-assisted radical prostatectomy (RARP) compared with laparoscopic radical prostatectomy (LRP) and of the Retzius-sparing (RS) technique over the traditional prostatectomy. Other techniques such as bladder neck and puboprostatic ligament (PPL) preservation, posterior reconstruction with or without combination of anterior suspension technique, and nerve-sparing (NS) approach seem to enhance EC. Oppositely, the endopelvic fascia preservation, bladder neck mucosa eversion/plication/slings, and the selective ligature of dorsal venous complex (DVC) were not significantly associated with EC improvements. RCTs are lacking on pubovesical complex-sparing, seminal vesicle preservation, anterior reconstruction of the puboprostatic collar, musculofascial reconstruction, and DVC suspension to the periosteum of the pubic bone techniques. Conclusions: RARP and RS have high-quality evidence supporting their ability to enhance postoperative EC recovery. NS, bladder neck, and PPL preservation may contribute to better EC recovery, although the evidence level is low. Further multicenter RCTs are needed to establish the optimal combination of standard surgical techniques. A new continence outcome-reporting standardization was proposed.

6.
Eur Urol ; 83(3): 249-256, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36604276

RESUMEN

BACKGROUND: Prostate magnetic resonance imaging (MRI) is now standard for assessment of suspected prostate cancer (PCa). A variety of approaches to MRI-based targeting has revolutionised prostate biopsies. OBJECTIVE: To describe the procedure and show the accuracy and tolerability of a novel Vector MRI/ultrasound fusion transperineal (TP) biopsy technique that uses electromagnetic (EM) needle tracking under local anaesthesia (LA). DESIGN, SETTING, AND PARTICIPANTS: Vector prostate biopsy using BiopSee fusion software, EM tracking technology, and transrectal ultrasound was performed in 69 patients meeting the biopsy criteria in two UK centres between September 2020 and August 2022. SURGICAL PROCEDURE: Stepper-mounted rectal ultrasound images were fused with MRI scans. LA was applied into two defined perineal tracks and a needle sheath with an EM sensor was inserted. The biopsy needle was directed precisely through the sheath to MRI targets under EM tracking. Biopsies were taken without antibiotic prophylaxis. MEASUREMENTS: Cancer detection (any PCa; grade group ≥2), side effects, and patient experience measures were recorded. RESULTS AND LIMITATIONS: Cancer detection in patients with Likert 4-5 lesions was 98% for any PCa and 83% for grade group ≥2. According to the 50 questionnaires returned, 42 patients (84%) reported no or minimal pain, while 40 (80%) reported no or minimal discomfort. No episodes of postoperative urinary retention occurred, and only one patient required treatment for infection. Limitations include the low patient number and incomplete responses to questionnaires. CONCLUSIONS: This novel Vector technique provides a feasible and tolerable procedure for MRI/ultrasound fusion TP biopsy under LA, with high cancer detection rates. This is achieved while maintaining patient comfort and with minimal rates of complications. PATIENT SUMMARY: We report a novel technique that uses electromagnetic needle tracking to perform highly accurate and comfortable prostate biopsies through the perineum under local anaesthetic.


Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Anestesia Local , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Ultrasonografía Intervencional/métodos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos
7.
Clin Genitourin Cancer ; 21(1): 162-170, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35970760

RESUMEN

INTRODUCTION: Clinically significant prostate cancer (csCaP) with Gleason ≥3 + 4 is found in 10% negative prebiopsy multiparametric (mp) MRI cases and varies widely for equivocal mpMRI cases. The objective of this study was to investigate long-term outcomes of patients with negative and equivocal mpMRIs and to develop a predictive score for csCaP risk stratification in this group. PATIENTS AND METHODS: Patients who underwent an upfront mpMRI between May 2015 and March 2018 with an MRI score Likert 1 to 3 were included in the study. Patients had either a CaP diagnosis at MRI-targeted biopsy or were not diagnosed and attended follow-up in the community. Outcomes were analysed through the Kaplan-Meier estimator and Cox Model. Regression coefficients of significant variables were used to develop a Risk of significant Cancer of the Prostate score (RosCaP). RESULTS: At first assessment 281/469 patients had mpMRI only and 188/469 mpMRI and biopsy, 26 csCaP were found at biopsy, including 10/26 in Likert 3 patients. 12/371 patients discharged without CaP after first assessment were diagnosed with csCaP during a median of 34.2 months' follow-up, 11/12 diagnosis occurred in patients omitting initial biopsy. csCaP diagnosis-free survival was 95.7% in the MRI group and 99.1% in the biopsy group. From these outcomes, a continuous RosCaP score was developed: RosCaP = 0.083 x Age - 0.202 x (1/PSA Density) + 0.786 (if Likert 3), and 4 risk classes were proposed. Limitations include retrospective design and absence of external validation. CONCLUSION: Age, PSA Density and MRI Likert score were significantly associated to the risk of csCaP and utilised to devise the novel RosCap predictive score focused to support risk assessment in patients with negative or equivocal mpMRI results.


Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Lactante , Próstata/diagnóstico por imagen , Próstata/patología , Antígeno Prostático Específico , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Factores de Riesgo
8.
J Clin Oncol ; 40(31): 3668, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35787066
9.
JAMA Cardiol ; 7(7): 690-698, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35612860

RESUMEN

Importance: Treatment of ST-segment elevation myocardial infarction (STEMI) in rural settings involves thrombolysis followed by transfer to a percutaneous coronary intervention-capable hospital. The first step is accurate diagnosis via electrocardiography (ECG), but one-third of all STEMI incidents go unrecognized and hence untreated. Objective: To reduce missed diagnoses of STEMI. Design, Setting, and Participants: This cluster randomized clinical trial included 29 hospital emergency departments (EDs) in rural Australia with no emergency medicine specialists, which were randomized to usual care vs automatically triggered diagnostic support from the tertiary referral hospital (management of rural acute coronary syndromes [MORACS] intervention). Patients presenting with symptoms compatible with acute coronary syndromes (ACS) were eligible for inclusion. The study was conducted from December 2018 to April 2020. Data were analyzed in August 2021. Intervention: Triage of a patient with symptoms compatible with ACS triggered an automated notification to the tertiary hospital coronary care unit. The ECG and point-of-care troponin results were reviewed remotely and a phone call was made to the treating physician in the rural hospital to assist with diagnosis and initiation of treatment. Main Outcomes and Measures: The proportion of patients with missed STEMI diagnoses. Results: A total of 6249 patients were included in the study (mean [SD] age, 63.6 [12.2] years; 48% female). Of 7474 ED presentations with suspected ACS, STEMI accounted for 77 (2.0%) in usual care hospitals and 46 (1.3%) in MORACS hospitals. Missed diagnosis of STEMI occurred in 27 of 77 presentations (35%) in usual care hospitals and 0 of 46 (0%) in MORACS hospitals (P < .001). Of eligible patients, 48 of 75 (64%) in the usual care group and 36 of 36 (100%) in the MORACS group received primary reperfusion (P < .001). In the usual care group, 12-month mortality was 10.3% (n = 8) vs 6.5% (n = 3) in the MORACS group (relative risk, 0.64; 95% CI, 0.18-2.23). Patients with missed STEMI diagnoses had a mortality of 25.9% (n = 7) compared with 2.0% (n = 1) for those with accurately diagnosed STEMI (relative risk, 13.2; 95% CI, 1.71-102.00; P = .001). Overall, there were 6 patients who did not have STEMI as a final diagnosis; 5 had takotsubo cardiomyopathy and 1 had pericarditis. There was no difference between groups in the rate of alternative final diagnosis. Conclusion and Relevance: The findings indicate that MORACS diagnostic support service reduced the proportion of missed STEMI and improved the rates of primary reperfusion therapy. Accurate diagnosis of STEMI was associated with lower mortality. Trial Registration: anzctr.org.au Identifier: ACTRN12619000533190.


Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/terapia , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/terapia , Factores de Tiempo
10.
J Clin Oncol ; 40(18): 2048-2057, 2022 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-35316080

RESUMEN

PURPOSE: The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses. METHODS: This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13. RESULTS: Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex. CONCLUSION: This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Capecitabina , Quimioterapia Adyuvante , Humanos , Pronóstico
11.
Br J Radiol ; 95(1131): 20210413, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34357796

RESUMEN

Prostate cancer (PCa) diagnostic and therapeutic work-up has evolved significantly in the last decade, with pre-biopsy multiparametric MRI now widely endorsed within international guidelines. There is potential to move away from the widespread use of systematic biopsy cores and towards an individualised risk-stratified approach. However, the evidence on the optimal biopsy approach remains heterogeneous, and the aim of this review is to highlight the most relevant features following a critical assessment of the literature. The commonest biopsy approaches are via the transperineal (TP) or transrectal (TR) routes. The former is considered more advantageous due to its negligible risk of post-procedural sepsis and reduced need for antimicrobial prophylaxis; the more recent development of local anaesthetic (LA) methods now makes this approach feasible in the clinic. Beyond this, several techniques are available, including cognitive registration, MRI-Ultrasound fusion imaging and direct MRI in-bore guided biopsy. Evidence shows that performing targeted biopsies reduces the number of cores required and can achieve acceptable rates of detection whilst helping to minimise complications and reducing pathologist workloads and costs to health-care facilities. Pre-biopsy MRI has revolutionised the diagnostic pathway for PCa, and optimising the biopsy process is now a focus. Combining MR imaging, TP biopsy and a more widespread use of LA in an outpatient setting seems a reasonable solution to balance health-care costs and benefits, however, local choices are likely to depend on the expertise and experience of clinicians and on the technology available.


Asunto(s)
Biopsia Guiada por Imagen/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Humanos , Imagen por Resonancia Magnética Intervencional/métodos , Masculino , Imagen Multimodal , Ultrasonografía/métodos
12.
Oncotarget ; 12(24): 2338-2350, 2021 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-34853657

RESUMEN

Prothrombin induced by vitamin K absence II (PIVKA-II) has recently been validated internationally as a diagnostic biomarker for hepatocellular carcinoma (HCC), as part of the GALAD model. However, its role as a treatment response biomarker has been less well explored. We, therefore, undertook a prospective study at a tertiary centre in the UK to evaluate the role of PIVKA-II as a treatment response biomarker in patients with early, intermediate and advanced stage HCC. In a cohort of 141 patients, we found that PIVKA-II levels tracked concordantly with treatment response in the majority of patients, across a range of different treatment modalities. We also found that rises in PIVKA-II levels almost always predated radiological progression. Among AFP non-secretors, PIVKA-II was found to be informative in 60% of cases. In a small cohort of patients undergoing liver transplantation, pre-transplant PIVKA-II levels predicted for microvascular invasion and poorer differentiation. Our results demonstrate the potential utility of PIVKA-II as a treatment response biomarker and in predicting microvascular invasion, in a Western population. PIVKA-II demonstrated improved performance over AFP but, as a single biomarker, its performance was still limited. Further larger prospective studies are recommended to evaluate PIVKA-II as a treatment response biomarker, within the GALAD model.

13.
J Clin Gastroenterol ; 55(2): 169-173, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32520885

RESUMEN

BACKGROUND: Recent studies have revealed that coadministration of gastric acid suppressants reduces the efficacy of the tyrosine kinase inhibitors erlotinib and sunitinib in patients with non-small cell lung cancer and renal cell carcinoma, respectively. The authors have therefore assessed if the concurrent use of gastric acid suppressants and sorafenib impairs outcomes in patients with advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted on all patients treated with sorafenib for advanced HCC at a single tertiary referral unit in the United Kingdom, between January 2008 and January 2014. A multivariate Cox proportional hazard model was used to assess the effect of the concomitant use of gastric acid suppression and sorafenib on progression-free survival (PFS) and overall survival (OS). RESULTS: Data were collected from 197 patients, of which 182 could be assessed for this study; 77 (42%) were on concurrent gastric acid suppression therapy. After adjusting for imbalances between the groups, a Cox regression analysis gave an adjusted hazard ratio for the concurrent acid suppression group compared with the no acid suppression group of 5.4 (95% confidence interval, 3.6-7.9) for PFS and 1.85 (95% confidence interval, 1.3-2.6) for OS. CONCLUSIONS: This single-center experience shows that patients with advanced HCC taking sorafenib and concomitant gastric acid suppression therapy have significantly inferior PFS and OS. This is the first time that this negative interaction has been reported and further prospective validation is warranted.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Hepáticas , Neoplasias Pulmonares , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Supervivencia sin Enfermedad , Ácido Gástrico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Niacinamida/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Estudios Retrospectivos , Sorafenib , Resultado del Tratamiento , Reino Unido
15.
Postgrad Med J ; 96(1142): 777-779, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32820086

RESUMEN

INTRODUCTION: Educational supervisors (ESs) play a critical role in the training of Foundation doctors. Many hospital trusts do not currently offer formal mechanisms to ensure the quality of supervision is at a high standard. Our Trust wanted to empower trainees to offer objective feedback on the quality of the supervisors. METHODS: We introduced a feedback form sent to all Foundation doctors at our Trust. The questionnaire was designed to identify whether ESs were meeting their responsibilities as defined by the Health Education England South West's Severn Deanery. We collected data throughout the academic year 2017-2018 (Year 1) as a pilot, before rolling out the definitive questionnaire with minor modifications from 2018 to 2019 (Year 2). RESULTS: All respondents met with their supervisor within the first month of the placement and 90.7% of the trainees found it easy to meet with their supervisor. The Trust received generally very good feedback for all of its supervisors. Low numbers (4/120 trainees) reported supervisors not engaging with the exception reporting process. CONCLUSION: Our Trust provides ESs of a high standard. The authors believe collecting feedback for ESs will achieve three things: 1) Drive up standards through increasing accountability of ESs receiving objective feedback. This will be of critical importance in the context of the severe acute respiratory syndrome coronavirus 2 pandemic and the changes to our work it has necessitated. 2) Empower trainees to make informed decisions about where they wish to train and under which supervisors. 3) Facilitate revalidation and appraisal for supervisors by collecting data from trainees on the quality of their supervision.


Asunto(s)
Actitud del Personal de Salud , Educación de Postgrado en Medicina/organización & administración , Docentes Médicos , Retroalimentación , Mejoramiento de la Calidad , Inglaterra , Hospitales de Distrito , Hospitales Generales , Humanos , Internado y Residencia , Encuestas y Cuestionarios
16.
Nature ; 583(7818): 807-812, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32669708

RESUMEN

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1-3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug-biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy-including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug-biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Marcadores Genéticos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Terapia Molecular Dirigida , Medicina de Precisión , Fumar/genética , Teorema de Bayes , Carcinoma de Pulmón de Células no Pequeñas/etiología , Protocolos Clínicos , Ensayos Clínicos como Asunto , Estudios de Cohortes , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/etiología , Oncogenes/genética , Selección de Paciente , Humo/efectos adversos , Triaje
17.
ACS Nano ; 14(6): 6906-6911, 2020 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-32453549

RESUMEN

Augmented reality and visual reality (AR and VR) microdisplays require micro light emitting diodes (µLEDs) with an ultrasmall dimension (≤5 µm), high external quantum efficiency (EQE), and narrow spectral line width. Unfortunately, dry etching which is the most crucial step for the fabrication of µLEDs in current approaches introduces severe damages, which seem to become an insurmountable challenge for achieving ultrasmall µLEDs with high EQE. Furthermore, it is well-known that µLEDs which require InGaN layers as an emitting region naturally exhibit significantly broad spectral line width, which becomes increasingly severe toward long wavelengths such as green. In this paper, we have reported a combination of our selective overgrowth approach developed very recently and epitaxial lattice-matched distributed Bragg reflectors (DBRs) embedded in order to address all these fundamental issues. As a result, our µLEDs with a diameter of 3.6 µm and an interpitch of 2 µm exhibit an ultrahigh EQE of 9% at ∼500 nm. More importantly, the spectral line width of our µLEDs has been significantly reduced down to 25 nm, the narrowest value reported so far for III-nitride green µLEDs.

18.
J Parkinsons Dis ; 10(3): 1087-1098, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32444563

RESUMEN

BACKGROUND: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. OBJECTIVE: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. METHODS: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. RESULTS: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. CONCLUSION: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.


Asunto(s)
Atención a la Salud , Práctica Clínica Basada en la Evidencia , Neurólogos , Enfermedad de Parkinson/terapia , Grupo de Atención al Paciente , Prioridad del Paciente , Atención Dirigida al Paciente , Guías de Práctica Clínica como Asunto , Centros de Atención Terciaria , Lista de Verificación , Consenso , Atención a la Salud/organización & administración , Atención a la Salud/normas , Práctica Clínica Basada en la Evidencia/organización & administración , Práctica Clínica Basada en la Evidencia/normas , Encuestas de Atención de la Salud , Humanos , Defensa del Paciente , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/normas , Atención Dirigida al Paciente/organización & administración , Atención Dirigida al Paciente/normas , Guías de Práctica Clínica como Asunto/normas , Centros de Atención Terciaria/organización & administración , Centros de Atención Terciaria/normas
19.
ACS Photonics ; 7(2): 411-415, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32296730

RESUMEN

A direct epitaxial approach to achieving ultrasmall and ultrabright InGaN micro light-emitting diodes (µLEDs) has been developed, leading to the demonstration of ultrasmall, ultraefficient, and ultracompact green µLEDs with a dimension of 3.6 µm and an interpitch of 2 µm. The approach does not involve any dry-etching processes which are exclusively used by any current µLED fabrication approaches. As a result, our approach has entirely eliminated any damage induced during the dry-etching processes. Our green µLED array chips exhibit a record external quantum efficiency (EQE) of 6% at ∼515 nm in the green spectral region, although our measurements have been performed on bare chips which do not have any coating, passivation, epoxy, or reflector, which are generally used for standard LED packaging in order to enhance extraction efficiency. A high luminance of >107 cd/m2 has been obtained on the µLED array bare chips. Temperature-dependent measurements show that our µLED array structure exhibits an internal quantum efficiency (IQE) of 28%. It is worth highlighting that our epitaxial approach is fully compatible with any existing microdisplay fabrication techniques.

20.
ACS Appl Mater Interfaces ; 12(11): 12949-12954, 2020 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-32090550

RESUMEN

To fully exploit the advantages of GaN for electronic devices, a critical electric field that approaches its theoretical value (3 MV/cm) is desirable but has not yet been achieved. It is necessary to explore a new approach toward the intrinsic limits of GaN electronics from the perspective of epitaxial growth. By using a novel two-dimensional growth mode benefiting from our high-temperature AlN buffer technology, which is different from the classic two-step growth approach, our high-electron-mobility transistors (HEMTs) demonstrate an extremely high breakdown field of 2.5 MV/cm approaching the theoretical limit of GaN and an extremely low off-state buffer leakage of 1 nA/mm at a bias of up to 1000 V. Furthermore, our HEMTs also exhibit an excellent figure-of-merit (Vbr2/Ron,sp) of 5.13 × 108 V2/Ω·cm2.

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