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2.
Fam Pract ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599778

RESUMO

BACKGROUND: Despite broad efforts to improve the reporting of biomedical research, no reporting guideline exists for primary care (PC) research. Little is known about current reporting practices or how well reports meet the needs of varied users in PC. OBJECTIVE: To map the published literature on PC research reporting: quality, strengths and weaknesses, recommendations and efforts to improve reporting. METHODS: Scoping review of literature across seven major databases and search engines to identify all articles on PC research reporting published in English, 2000-20. An additional secondary search of references of these 25 articles and consideration of expert panel suggestions. Structured data extraction by multiple reviewers using a predetermined form. RESULTS: Search yielded 2847 unique titles, of which 126 underwent full-text review and 25 met inclusion criteria. Publications included opinion pieces (9), systematic reviews (5), methods articles (2), literature reviews (4), qualitative studies (4) and surveys (1). Studies focussed on a variety of topics and research methods. All publications identified the need for improved reporting and recommended items to include in reports. Most commonly, publications cited the need for more detailed reporting on the context of study interventions, clinical settings and health care systems. Most publications endorsed the use of reporting guidelines and recognized the unique needs of PC research reporting. CONCLUSIONS: Published research and opinion identify unique needs for PC research reports and support new guidance to improve the validity, generalizability and application of study findings.

3.
Curr Oncol ; 28(1): 428-439, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450821

RESUMO

Background: Brain metastases are observed in more than 40% of all patients with stage 4 melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors have positively impacted outcomes in patients with metastatic melanoma.brain metastases. Here, we examined real world clinical outcomes of patients presenting with melanoma brain metastases (MBMs). Methods: This retrospective review evaluated MBMs patients treated at The Ottawa Hospital from April 2000 to July 2017. Clinical, radiologic, pathologic and treatment information were gathered from the electronic medical records. The primary outcome was overall survival. The proportional Cox regression model was employed for survival data, while the Fisher's exact and Mann-Whitney U tests analyzed the relationship between categorical and continuous data, respectively. Results: This retrospective study included 276 patients. Brain metastases were detected symptomatically in 191 patients (69.2%); the rates of detection by routine screening were 4.6% in the pre-2012 era and 11.7% in the contemporary era (p = 0.029). Median survival was three months. Predictors of overall survival were age, higher lactate dehydrogenase (LDH) values, multiple brain lesions, more extensive extracranial disease, neurological symptoms, infratentorial lesions and treatment type. Multivariable analysis demonstrated that stereotactic radiotherapy (STRT) was associated with a hazard ratio of 0.401 (p < 0.001) for survival; likewise, immune checkpoint inhibitor therapy was associated with a hazard ratio of 0.375 (p < 0.001). Conclusion: The findings from this study as "real world" data are consistent with results of pivotal clinical trials in MBMs patients and support contemporary locoregional and immunotherapy practices.

4.
J Am Board Fam Med ; 34(1): 12-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33452078

RESUMO

PURPOSE: To assess opportunities to improve reporting of primary care (PC) research to better meet the needs of its varied users. METHODS: International, interprofessional online survey of PC researchers and users, 2018 to 2019. Respondents used Likert scales to rate frequency of difficulties in interpreting, synthesizing, and applying PC research reports. Free-text short answers were categorized by template analysis to record experiences, concerns, and suggestions. Areas of need were checked across existing reporting guidelines. RESULTS: Survey yielded 255 respondents across 24 nations, including 138 women (54.1%), 169 physicians (60%), 32 scientists (11%), 20 educators (7%), and 18 public health professionals (6%). Overall, 37.4% indicated difficulties using PC research reports "50% or more of the time." The most common problems were synthesizing findings (58%) and assessing generalizability (42%). Difficulty was reported by 49% for qualitative, 46% for mixed methods, and 38% for observational research. Most users wanted richer reporting of theoretical foundation (53.7%); teams, roles, and organization of care (53.4%); and patient involvement in the research process (52.7%). Few reported difficulties with ethics or disclosure of funding or conflicts. Free-text answers described special challenges in reporting PC research: context of clinical care and setting; practical details of interventions; patient-clinician and team relationships; and generalizability, applicability and impact in the great variety of PC settings. Cross-check showed that few current reporting guidelines focus on these needs. CONCLUSIONS: Opportunities exist to improve the reporting of PC research to make it more useful for its many users, suggesting a role for a PC research reporting guideline.

5.
Thorac Surg Clin ; 31(1): 89-96, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33220775

RESUMO

Identifying the exact cause for persistent and recurrent neurogenic thoracic outlet syndrome (NTOS) is challenging even with high-resolution imaging of the thoracic outlet. Improvement can be achieved with redo first rib resection, although the posterior first rib remnant is one of several potential points of brachial plexus compression. In approaching reoperative surgery for NTOS, the aim is to provide complete thoracic outlet decompression as guided by the patient's history, physical examination, and adjunctive imaging. This may involve resection of the posterior first rib remnant, scar tissue encasing the brachial plexus, elongated C7 transverse process, cervical rib, and/or pectoralis minor tendon.

6.
Ann Thorac Surg ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33275934

RESUMO

BACKGROUND: The supraclavicular exposure represents an alternative approach for thoracic outlet decompression in neurogenic thoracic outlet syndrome (nTOS) with unique access to neurovascular structures. We aimed to evaluate the learning curve for this approach and associated patient outcomes. METHODS: Patients undergoing first-time, unilateral, supraclavicular thoracic outlet decompression for nTOS were included. Cumulative-sum and linear-spline-regression analyses were used to determine the operative time learning curve. Patients were consecutively organized into early (learning phase) and late (competency) cohorts. Primary endpoints were the operative time learning curve operation number and association of this learning curve on differences in self-reported postoperative symptomatic improvement between early and late cohorts, adjusting for American Society of Anesthesiology classification, body mass index, previous treatment (opioid/neuropathic medication/botulinum-injection), and length-of-stay. RESULTS: Among 114 patients, learning curve analyses showed decreasing operative times, plateauing at the 51st operation (ß=-1.63 [-2.30,-0.95], p<0.001). No periprocedural differences existed between early (operations 1-50) and late (operations 51-114) cohorts. Self-reported 90-day outcomes were similar in early and late cohorts (odds ratio [OR]: 1.60 95%CI [0.65,3.95], p=0.31). Mediators of poor self-reported outcomes included increasing American Society of Anesthesiology classification (OR 0.21 [0.08,0.54], p=0.001), failed preoperative botulinum-injection (OR 0.15 [0.03,0.65], p=0.01), and increased length-of-stay (OR 0.40 [0.22,0.73], p=0.003). CONCLUSIONS: The learning curve for supraclavicular thoracic outlet decompression in nTOS occurred after 51 operations with a trend towards improved 90-day self-reported outcomes from the early to late phases. These findings, along with mediators of poorer outcomes, may aid surgeons in adopting a new approach and counseling patients on expected outcomes.

7.
J Phys Chem Lett ; : 157-164, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320682

RESUMO

Knowledge of structural and thermal properties of molten salts is crucial for understanding and predicting their stability in many applications such as thermal energy storage and nuclear energy systems. Probing the behavior of metal contaminants in molten salts is presently limited to either foreign ionic species or metal nanocrystals added to the melt. To bridge the gap between these two end states and follow the nucleation and growth of metal species in molten salt environment in situ, we use synchrotron X-rays as both a source of solvated electrons for reducing Ni2+ ions added to ZnCl2 melt and as an atomic-level probe for detecting formation of zerovalent Ni nanoparticles. By combining extended X-ray absorption fine structure analysis with X-ray absorption near edge structure modeling, we obtained the average size and structure of the nanoparticles and proposed a radiation-induced reduction mechanism of metal ions in molten salts.

8.
J Nucl Med Technol ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33361187

RESUMO

RATIONALE: A new protocol for rapid SPECT/CT blood pool imaging consisting of fewer image angle acquisitions was evaluated for localization of focal sites of soft tissue inflammation, infection and osteomyelitis. Methods: Immediately following dynamic flow and standard planar blood pool imaging with 99mTc-MDP, fewer angle SPECT/CT (FASpecT/CT) was performed with a dual head gamma camera consisting of 6 steps over 360°, 12 total images with 30° separation between angles and 30 seconds per image requiring a total imaging time of approximately 3 minutes. Images were reconstructed using ordered subset expectation maximization (OSEM) iterative reconstruction. Prior to use in a patient-care setting, various FASpecT/CT acquisition protocols were modeled using a phantom to determine the minimum number of stops and stop duration required to produce a reliable image. Results: FASpecT/CT blood pool images provided excellent 3-dimensional localization of spine osteomyelitis, soft tissue infection of the foot and tendonitis of the hand and foot utilizing a 3 minute image acquisition time. FASpecT/CT acquisition protocol required 1.3-3.5 minutes including camera movement time. This was a reduction of 72-90% when compared to the time required for the standard 60 angle, 20 second SPECT/CT acquisition. Principal Conclusion: FASpecT/CT blood pool images help localize focal sites of hyperemia/inflammation which can increase exam sensitivity and specificity. Additionally, utilizing a FASpecT/CT imaging protocol decreases imaging time by up to 90%.

9.
Ann Thorac Surg ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33181131

RESUMO

BACKGROUND: This study sought to examine the impact of nodule density on recurrence and survival in female patients with lung adenocarcinoma treated by lobectomy or sublobar resection. METHODS: Retrospective study of female patients who underwent surgical resection for pathologic stage IA adenocarcinoma. Patients with preoperative imaging were included for analysis if the consolidation/tumor ratio (CTR) was 0.5 (solid-predominant GGO) to 1.0 (solid). Kaplan-Meier curves were generated to estimate overall survival (OS) and disease-free survival (DFS). Risk estimates were calculated using multivariable Cox proportional hazards models. RESULTS: For all patients (n=357), sublobar resection demonstrated worse 5-year DFS compared to lobectomy (76.4% vs 67.9%, p=0.05). Multivariable modeling showed worse DFS with sublobar resection (HR 1.55, p=0.06), and tumors > 2 cm (HR 2.32, p=0.05). On radiologic evaluation, the solid-predominant GGO group (n=81) demonstrated a smaller solid component compared to the solid nodule group (n=163) (1.49 cm vs. 1.84 cm, p<0.001), yet comparable total size. The solid-predominant GGO group showed improved 5-year OS (90.8 vs 76.8, p=0.01) and DFS (79.3 vs 67.2, p=0.05) compared to the solid nodule group. Additionally, the solid-predominant GGO group demonstrated equivalent OS (90.8% vs 90.8%, p=0.93) and DFS (76.0% vs 81.7%, p=0.60) with sublobar resection compared to lobectomy. CONCLUSIONS: In this report of female patients with stage IA adenocarcinoma, sublobar resection was associated with worse DFS compared to lobectomy in whole group analysis. However, patients with solid-predominant GGOs demonstrate improved 5-year OS and DFS compared to solid nodules with equivalent outcomes regardless of resection type.

10.
Br J Sports Med ; 54(24): 1482-1487, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33239354

RESUMO

OBJECTIVES: We assess the potential benefits of increased physical activity for the global economy for 23 countries and the rest of the world from 2020 to 2050. The main factors taken into account in the economic assessment are excess mortality and lower productivity. METHODS: This study links three methodologies. First, we estimate the association between physical inactivity and workplace productivity using multivariable regression models with proprietary data on 120 143 individuals in the UK and six Asian countries (Australia, Malaysia, Hong Kong, Thailand, Singapore and Sri Lanka). Second, we analyse the association between physical activity and mortality risk through a meta-regression analysis with data from 74 prior studies with global coverage. Finally, the estimated effects are combined in a computable general equilibrium macroeconomic model to project the economic benefits of physical activity over time. RESULTS: Doing at least 150 min of moderate-intensity physical activity per week, as per lower limit of the range recommended by the 2020 WHO guidelines, would lead to an increase in global gross domestic product (GDP) of 0.15%-0.24% per year by 2050, worth up to US$314-446 billion per year and US$6.0-8.6 trillion cumulatively over the 30-year projection horizon (in 2019 prices). The results vary by country due to differences in baseline levels of physical activity and GDP per capita. CONCLUSIONS: Increasing physical activity in the population would lead to reduction in working-age mortality and morbidity and an increase in productivity, particularly through lower presenteeism, leading to substantial economic gains for the global economy.

11.
J Cogn Neurosci ; : 1-9, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054551

RESUMO

Pupillometry has been found to be correlated with activity of cholinergic and noradrenergic neuromodulator systems. These systems regulate the level of cortical arousal and therefore perception, attention, and memory. Here, we tested how different types of pupil size variance (prestimulus baseline and prestimulus hippus power) may correlate with behavioral and electrophysiological brain responses (ERPs). We recorded pupil size and ERPs while participants were presented with a series of words and then asked whether they had been in the initial list when they were later presented intermixed with unpresented words. We found that a smaller prestimulus baseline pupil size during the study phase was associated with better memory performance. Study items also evoked a larger P3 response at presentation and a greater old/new memory ERP effect at test when prestimulus pupil size was small rather than large. Prestimulus hippus power was found to be a between-subjects factor affecting the robustness of memory encoding with less power being associated with a greater old/new memory ERP effect. These results provide evidence relating memory and ERPs to variables defined on pupil size that are thought to reflect varying states of parasympathetic and sympathetic arousal.

12.
Biophys J ; 119(10): 2045-2054, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33091377

RESUMO

Gene regulation by control of transcription initiation is a fundamental property of living cells. Much of our understanding of gene repression originated from studies of the Escherichia coli lac operon switch, in which DNA looping plays an essential role. To validate and generalize principles from lac for practical applications, we previously described artificial DNA looping driven by designed transcription activator-like effector dimer (TALED) proteins. Because TALE monomers bind the idealized symmetrical lac operator sequence in two orientations, our prior studies detected repression due to multiple DNA loops. We now quantitatively characterize gene repression in living E. coli by a collection of individual TALED loops with systematic loop length variation. Fitting of a thermodynamic model allows unequivocal demonstration of looping and comparison of the engineered TALED repression system with the natural lac repressor system.

13.
Neurosci Biobehav Rev ; 119: 440-455, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33002561

RESUMO

Dreams are internally generated experiences that occur independently of current sensory input. Here we argue, based on cortical anatomy and function, that dream experiences are tightly related to the workings of a specific part of cortical pyramidal neurons, the apical integration zone (AIZ). The AIZ receives and processes contextual information from diverse sources and could constitute a major switch point for transitioning from externally to internally generated experiences such as dreams. We propose that during dreams the output of certain pyramidal neurons is mainly driven by input into the AIZ. We call this mode of functioning "apical drive". Our hypothesis is based on the evidence that the cholinergic and adrenergic arousal systems, which show different dynamics between waking, slow wave sleep, and rapid eye movement sleep, have specific effects on the AIZ. We suggest that apical drive may also contribute to waking experiences, such as mental imagery. Future studies, investigating the different modes of apical function and their regulation during sleep and wakefulness are likely to be richly rewarded.

14.
Rev Sci Instrum ; 91(8): 083105, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32872908

RESUMO

To facilitate the development of molten salt reactor technologies, a fundamental understanding of the physical and chemical properties of molten salts under the combined conditions of high temperature and intense radiation fields is necessary. Optical spectroscopic (UV-Vis-near IR) and electrochemical techniques are powerful analytical tools to probe molecular structure, speciation, thermodynamics, and kinetics of solution dynamics. Here, we report the design and fabrication of three custom-made apparatus: (i) a multi-port spectroelectrochemical furnace equipped with optical spectroscopic and electrochemical instrumentation, (ii) a high-temperature cell holder for time-resolved optical detection of radiolytic transients in molten salts, and (iii) a miniaturized spectroscopy furnace for the investigation of steady-state electron beam effects on molten salt speciation and composition by optical spectroscopy. Initial results obtained with the spectroelectrochemical furnace (i) and high-temperature cell holder (ii) are reported.

15.
Cancer Res ; 80(20): 4324-4334, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32928922

RESUMO

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in TP53 (87%) and KRAS (73%), amplification of MYC (47%), and homozygous deletion of CDKN2A (40%) that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of three ASCP and three PDAC genomes using flow-sorted PDX models identified genes with accessible chromatin unique to the ASCP genomes, including the lysine methyltransferase SMYD2 and the pancreatic cancer stem cell regulator RORC in all three ASCPs, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes in a single ASCP. Finally, we demonstrate significant activity of a pan FGFR inhibitor against organoids derived from the FGFR1-ERLIN2 fusion-positive ASCP PDX model. Our results suggest that the genomic and epigenomic landscape of ASCP provide new strategies for targeting this aggressive subtype of pancreatic cancer. SIGNIFICANCE: These data provide a unique description of the ASCP genomic and epigenomic landscape and identify candidate therapeutic targets for this dismal cancer.

16.
Spine Deform ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32946067

RESUMO

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: To compare complications before and after implementation of the Multi-D screening protocol in complex pediatric patients undergoing spinal instrumentation for non-idiopathic scoliosis. Pediatric patients undergoing surgery for non-idiopathic scoliosis experience significantly more complications than those with idiopathic scoliosis. Operating on these patients can lead to serious complications including death. Recent reports have demonstrated the benefits of establishing a multidisciplinary-based system to reduce complications in adult spinal deformity during the perioperative period. However, there are limited studies examining these benefits in a complex pediatric spine population. METHODS: This was a retrospective review of all cases involving spinal instrumentation at our institution for 2 years before and after the initiation of our Neuromuscular Spine Surgery Care Plan in July 2014. Study sample was n = 129 cases (107 patients) prior to the initiation of the process and n = 122 cases (109 patients) thereafter. Primary outcome measures included: mortality at 30 days and 1 year; post-operative neurologic deficit, and surgical site infections (SSI). Secondary outcome measures included: instrument failure in 1 year; readmission in 30 days; return to OR in 90 days. RESULTS: The study populations were matched by age and gender. Patients passing the Multi-D conference had higher BMI. Implementation of the Multi-D conference reduced mortality at 30 days (2 vs 0, p = 0.17) and at 1 year (4 vs 0, p = 0.04), as well as reduced post-operative neurologic deficit (2 vs 0, p = 0.17). The rate of SSI remained unchanged. All other secondary outcome measures also remained unchanged. CONCLUSIONS: Implementation of a Multi-D conference led to a significant reduction in mortality at 1 year, and is an important safety process to reduce serious complications after non-idiopathic scoliosis surgery. LEVEL OF EVIDENCE: Level III.

17.
Ann Surg ; 272(4): 583-588, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32657925

RESUMO

OBJECTIVE: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification. BACKGROUND: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease. METHODS: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC. RESULTS: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1 mg compared to <1 mg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22). CONCLUSIONS: SLN(s) are more reliably identified with ICG dose ≥1 mg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Corantes , Humanos , Verde de Indocianina , Estudos Retrospectivos
18.
Pediatr Blood Cancer ; 67(9): e28429, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32672885

RESUMO

Extracorporeal membrane oxygenation (ECMO) may be used in extreme circumstances for patients with a mediastinal mass and respiratory failure. We report on a young man with primary mediastinal B-cell lymphoma invading into the trachea, requiring a 40-day ECMO run who underwent fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and treatment with concurrent mediastinal irradiation and continuous infusion chemotherapy while on this life-saving technology. This case illustrates that oncology patients may be managed by multidisciplinary teams for extended periods in extraordinary circumstances using multimodality therapies. Additionally, to our knowledge this is the first case to demonstrate the feasibility of FDG-PET imaging while on ECMO.


Assuntos
Quimiorradioterapia , Oxigenação por Membrana Extracorpórea , Fluordesoxiglucose F18/administração & dosagem , Linfoma de Células B , Neoplasias do Mediastino , Tomografia por Emissão de Pósitrons , Adolescente , Humanos , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/terapia , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/terapia
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