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1.
Clin Teach ; : e13776, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38711395

RESUMO

BACKGROUND: Health care delivery contributes a significant carbon footprint in the United Kingdom, and paradoxically climate change is linked to poorer human health outcomes. New General Medical Council (GMC) requirements mandate medical graduates must be able to apply sustainable care to their practice. Implementation of sustainable health care (SHC) teaching is a new challenge for medical schools, and there are several identified barriers including an overcrowded curriculum, lack of expertise within faculties, lack of institutional support and inadequate assessment techniques. APPROACH: We established a new SHC curriculum spiralling throughout the overall medical curriculum, and as part of this introduced a sustainable quality improvement (susQI) project to our final year cohort. SusQI considers the environmental, social and financial impacts as well as patient and population outcomes. Our students undertook this in their final year GP assistantships. EVALUATION: We sought multi-sourced data through focus groups, formal end of placement feedback, informal feedback and external feedback. We applied thematic analysis to focus group transcriptions and triangulated with the other data sources. We identified some common themes: First, susQI was enjoyed and valuable; second, it allowed meaningful participation; third, it created a co-learning environment; and fourth, timing and curriculum placement are important when integrating susQI. IMPLICATIONS: SusQI can implement SHC into the overcrowded medical curriculum in a low cost, low resource manner without the need for experienced faculty. SusQI is empowering for students and grants them an active team role. Expansion into secondary and tertiary care is feasible, and we contend that susQI can be placed in other health care curricula.

2.
J Environ Manage ; 358: 120768, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599081

RESUMO

Urbanization changes land cover through the expansion of impermeable surfaces, leading to a significant rise in runoff, sediment, and nutrient loading. The quality of stormwater is related to land use and is highly variable. Currently, stormwater is predominantly described through watershed models that rely minimally, if at all, on field monitoring data. The simple event mean concentration (EMC) wash-off approach by land use is a common method for estimating urban runoff loads. However, a major drawback of the EMC approach is it assumes concentration remains constant across events for a specific land use. Build-up/wash-off equations have been formulated to consider variations in concentration between events. However, several equation parameters are challenging to estimate, making them difficult to use. We conducted a monitoring and modeling study and investigated the impact of land use on stormwater quantity and quality and optimized and investigated the build-up/wash-off parameters for three homogenous urban land uses to estimate nutrients (nitrogen and phosphorus) and sediment loads. Stormwater from commercial, medium-density residential, and transportation land uses was sampled using automatic samplers during storm events, and water quality was characterized for a variety of them for 14 months. Analysis of stormwater samples included assessments for total nitrogen, total phosphorus, and total suspended solids. Results showed that medium-density residential land use had the highest median total nitrogen and total phosphorus event mean concentrations and commercial had the highest median total suspended solids EMCs. Water quality parameters (or build-up/wash-off parameters) exhibited significant variation between land uses, confirming that land use is a key determinant of stormwater quality. The median particle size for each land use was less than 150 µm, indicating that the most common particle size in stormwater was a very fine sand or smaller. This small size should be considered by stakeholders in the design of stormwater treatment systems.


Assuntos
Fósforo , Qualidade da Água , Fósforo/análise , Sedimentos Geológicos/análise , Chuva , Urbanização , Monitoramento Ambiental/métodos , Nutrientes/análise , Movimentos da Água , Nitrogênio/análise
3.
EMBO Rep ; 25(5): 2202-2219, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600346

RESUMO

Neural progenitor cells within the cerebral cortex undergo a characteristic switch between symmetric self-renewing cell divisions early in development and asymmetric neurogenic divisions later. Yet, the mechanisms controlling this transition remain unclear. Previous work has shown that early but not late neural progenitor cells (NPCs) endogenously express the autism-linked transcription factor Foxp1, and both loss and gain of Foxp1 function can alter NPC activity and fate choices. Here, we show that premature loss of Foxp1 upregulates transcriptional programs regulating angiogenesis, glycolysis, and cellular responses to hypoxia. These changes coincide with a premature destabilization of HIF-1α, an elevation in HIF-1α target genes, including Vegfa in NPCs, and precocious vascular network development. In vitro experiments demonstrate that stabilization of HIF-1α in Foxp1-deficient NPCs rescues the premature differentiation phenotype and restores NPC maintenance. Our data indicate that the endogenous decline in Foxp1 expression activates the HIF-1α transcriptional program leading to changes in the tissue environment adjacent to NPCs, which, in turn, might alter their self-renewal and neurogenic capacities.


Assuntos
Córtex Cerebral , Fatores de Transcrição Forkhead , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células-Tronco Neurais , Proteínas Repressoras , Transdução de Sinais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Animais , Camundongos , Córtex Cerebral/metabolismo , Córtex Cerebral/citologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Neovascularização Fisiológica/genética , Diferenciação Celular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Neurogênese/genética , Glicólise , Angiogênese
4.
Acad Med ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363814

RESUMO

PURPOSE: A growing number of health systems are establishing learning health system (LHS) programs, where research focuses on rapidly improving the health system's internal operations and performance. The authors examine funding challenges facing such initiatives and identify strategies for managing tensions between reliance on external research funding and directly contributing to improvement and learning within the researchers' own system. METHOD: Qualitative case studies of LHS research programs in 5 health systems were performed via 38 semistructured interviews (October 2019-April 2021) with 35 diverse respondents. Inductive and deductive rapid qualitative analysis supported interview, system-level, and cross-system summaries and analysis. RESULTS: External funding awards to LHS researchers facilitated some internal improvement and learning, scientific advancements, and the reputation of researchers and their systems. But reliance on external funding also challenged researchers' responsiveness to concerns of system leaders, managers, practitioners, and system needs. Gaps between external funding requirements and internally focused projects arose in objectives, practical applicability, audiences, timetables, routines, skill sets, and researchers' careers. To contribute more directly to system improvement LHS researchers needed to collaborate with clinicians and other nonresearchers and pivot between long research studies and shorter, dynamic improvement, evaluation, and data analysis projects. With support from system executives, LHS program leaders employed several strategies to enhance researchers' internal contributions. They aligned funded-research topics with long-term system needs, obtained internal funding for implementing and sustaining practice change, and diversified funding sources. CONCLUSIONS: To foster LHS research contributions to internal system learning and improvement, LHS program leaders need to manage tensions between concentrating on externally funded research and fulfilling their mission of providing research-based services to their own system. Health system executives can support LHS programs by setting clear goals for them; appropriately staffing, budgeting, and incentivizing LHS researchers; and developing supportive, systemwide teamwork, skill development programs, and data infrastructures.

5.
European J Pediatr Surg Rep ; 12(1): e33-e37, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38312432

RESUMO

Esophageal atresia (EA) repair can be complicated by associated malformations such as a tracheobronchial remnant in the distal esophagus. We describe our experience with a patient found to have long-gap EA with a distal cartilaginous ring who was managed using a combination of esophageal lengthening and magnetic compression anastomosis. A 5-month-old girl was referred to us from an outside hospital with type C EA including a very high upper pouch. She had undergone a prior thoracotomy with fistula ligation during which a clip was placed on the lower esophagus, leaving a 2-cm diverticulum on the trachea and a short lower esophageal pouch. Upon endoscopic evaluation at our center, we found a tracheobronchial remnant in the lower esophagus between the clip and the carina. An open thoracotomy was performed to approximate the esophageal pouches and a magnet anchor (Connect EA, Myka Laboratories, San Francisco, California, United States) was placed retrograde through the distal esophageal cartilaginous ring into the lower pouch. On postoperative day 8, after adequate growth and decreased pouch tension, a second magnetic anchor was placed endoscopically to the upper pouch to mate with the previously placed lower pouch anchor. The anastomosis formed within 14 days. Due to the tracheobronchial remnant, the device did not pass distally and was removed endoscopically. On postoperative day 8, balloon dilation of the anastomosis and tracheobronchial remnant was performed. Subsequently, the patient required a total of 6 dilations in an 18-month follow-up. This case report illustrates the utility of using magnets to create an esophageal anastomosis in complex cases of EA with concomitant esophageal malformations. The parents of the patient gave their written consent to publish this technical report.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38388778

RESUMO

Combined androgen deprivation therapy (ADT) and radiotherapy (RT) improves outcomes for intermediate and high-risk prostate cancer. Treatment intensification with abiraterone acetate/prednisone (AAP) provides additional benefit for high-risk disease. We previously reported 3-year outcomes of a single-arm prospective multicenter trial (AbiRT trial) of 33 patients with unfavorable intermediate risk (UIR) and favorable high risk (FHR) prostate cancer undergoing short course, combination therapy with ADT, AAP, and RT. Here we report the final analysis demonstrating a high rate of testosterone recovery (97%) and excellent biochemical progression-free survival (97%) at 5 years. These data support comparative prospective studies of shorter, more potent ADT courses in favorable high-risk prostate cancer.

8.
Aerosp Med Hum Perform ; 95(2): 123-131, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38263098

RESUMO

INTRODUCTION: Human access to space is expanding rapidly in the commercial environment, with various private companies offering commercial flights to spaceflight participants (SFPs). SFPs are more likely than career astronauts to have medical conditions novel to spaceflight and may not have undergone as rigorous a medical screening process as that used for career astronauts, representing new and unstudied risks in the spaceflight environment. We report participation of a subject with recent median sternotomy for aortic valve replacement and atrial septal defect closure in centrifuge-simulated dynamic phases of orbital and suborbital spaceflight.CASE REPORT: A 40-yr-old man with a history of congenital bicuspid aortic valve and atrial septal defect with successful repair 8 mo prior participated in an ongoing human centrifuge research study. The subject had the opportunity to participate in up to five centrifuge runs in an 8-h period, with profiles simulating commercial spaceflight. Maximum exposures included +4.0 Gz, +4.5 Gx, 6.1 G resultant, and maximum onset rate < 0.5 Gz · s-1 and +1 Gx · s-1. Physiological data acquisition included hemodynamics, electrocardiogram, neurovestibular exams, and postrun questionnaires covering motion sickness, disorientation, and similar. The subject tolerated the physiological aspects of hypergravity well, noting progressive sternal pain with increasing +Gx, ultimately leading him to opt out of the final profile.DISCUSSION: Postcardiothoracic surgery risks to SFPs are largely unknown, especially within 12 mo of a significant surgical procedure. This case provides an approach for risk stratification, preparticipation evaluation, and medical management of a postsurgical patient with significant cardiac history in spaceflight and analog environments.Fernandez WL, Blue RS, Harrison MF, Powers W, Shah R, Auñón-Chancellor S. Centrifuge-simulated spaceflight after aortic valve replacement and atrial septal defect repair. Aerosp Med Hum Perform. 2024; 95(2):123-131.


Assuntos
Comunicação Interatrial , Hipergravidade , Voo Espacial , Humanos , Masculino , Valva Aórtica , Astronautas
10.
Contemp Clin Trials ; 136: 107388, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37972755

RESUMO

BACKGROUND: Those with intermediate and high-risk prostate cancer typically receive androgen deprivation therapy (ADT) as part of their treatment. ADT often results in extensive side effects including increased risk of cardiometabolic disease. Many ADT side effects can be influenced by exercise, both resistance and aerobic training. Exercise regimes typically combine aerobic and resistance exercise but the appropriate emphasis for achieving the broadest range of therapeutic benefits has yet to be determined. We propose to determine the feasibility of undertaking a larger trial comparing a resistance- vs an aerobic-emphasised exercise intervention in men with prostate cancer undergoing ADT. The trial will also investigate preliminary evidence of difference between arms for cardiometabolic health and quality of life outcomes. METHODS: This is a 6-month randomised two-armed feasibility trial. Prostate cancer patients undergoing ADT and radiotherapy will be recruited (n = 24) and randomised to either a resistance- or aerobic-emphasised group. Participants will attend twice-weekly supervised individual or small group sessions, with 75% of exercise time in the primary exercise modality. The primary outcome will be feasibility, determined via assessment of recruitment, retention, adherence, safety, and acceptability. Secondary outcomes will include quality of life, body composition, vascular indices, aerobic and muscular fitness and cardiometabolic health blood biomarkers. CONCLUSION: It is envisaged that the trial will provide valuable information and preliminary difference data that will aid in the design of an efficacious larger trial that will adopt a major and minor emphasis approach to the scheduling of resistance and aerobic exercise.


Assuntos
Doenças Cardiovasculares , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Androgênios , Doenças Cardiovasculares/epidemiologia , Exercício Físico , Terapia por Exercício/métodos , Estudos de Viabilidade , Força Muscular , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Pediatr Surg ; 59(3): 437-444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37838619

RESUMO

INTRODUCTION: Delayed primary repair of esophageal atresia in patients with high-risk physiologic and anatomic comorbidities remains a daunting challenge with an increased risk for peri-operative morbidity and mortality via conventional repair. The Connect-EA device facilitates the endoscopic creation of a secure esophageal anastomosis. This follow-up study reports our long-term outcomes with the novel esophageal magnetic compression anastomosis (EMCA) Connect-EA device for EA repair, as well as lessons learned from the ten first-in-human cases. We propose an algorithm to maximize the advantages of the device for EA repair. METHODS: Under compassionate use approval, from June 2019 to December 2022, ten patients with prohibitive surgical or medical risk factors underwent attempted EMCA with this device. All patients underwent prior gastrostomy, tracheoesophageal fistula ligation (if necessary), and demonstrated pouch apposition prior to EMCA. RESULTS: Successful device deployment and EMCA formation were achieved in nine patients (90%). Mean time to anastomosis formation was 8 days (range 5-14) and the device was retrieved endoscopically in five (56%) cases. At median follow-up of 22 months (range 4-45), seven patients (78%) are tolerating oral nutrition. Balloon dilations (median 4, range 1-11) were performed either prophylactically for radiographic asymptomatic anastomotic narrowing (n = 7, 78%) or to treat clinically-significant anastomotic narrowing (n = 2, 22%) with no ongoing dilations at 3-month follow up post-repair. CONCLUSION: EMCA with the Connect-EA device is a safe and feasible minimally-invasive alterative for EA repair in high-risk surgical patients. Promising post-operative outcomes warrant further Phase I investigation. LEVEL OF EVIDENCE: IV, Case series of novel operative technique without comparison group.


Assuntos
Acetatos , Atresia Esofágica , Fístula Traqueoesofágica , Humanos , Atresia Esofágica/cirurgia , Ensaios de Uso Compassivo , Seguimentos , Anastomose Cirúrgica/métodos , Resultado do Tratamento , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
13.
Obes Surg ; 34(2): 515-523, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38135738

RESUMO

PURPOSE: Metabolic surgery remains underutilized for treating type 2 diabetes, as less invasive alternative interventions with improved risk profiles are needed. We conducted a pilot study to evaluate the feasibility of a novel magnetic compression device to create a patent limited caliber side-to-side jejunoileal partial diversion in a nonhuman primate model. MATERIALS AND METHODS: Using an established nonhuman primate model of diet-induced insulin resistance, a magnetic compression device was used to create a side-to-side jejunoileal anastomosis. Primary outcomes evaluated feasibility (e.g., device mating and anastomosis patency) and safety (e.g., device-related complications). Secondary outcomes evaluated the device's ability to produce metabolic changes associated with jejunoileal partial diversion (e.g., homeostatic model assessment of insulin resistance [HOMA-IR] and body weight). RESULTS: Device mating, spontaneous detachment, and excretion occurred in all animals (n = 5). There were no device-related adverse events. Upon completion of the study, ex vivo anastomoses were widely patent with healthy mucosa and no evidence of stricture. At 6 weeks post-device placement, HOMA-IR improved to below baseline values (p < 0.05). Total weight also decreased in a linear fashion (R2 = 0.97) with total weight loss at 6 weeks post-device placement of 14.4% (p < 0.05). CONCLUSION: The use of this novel magnetic compression device to create a limited caliber side-to-side jejunoileal anastomosis is safe and likely feasible in a nonhuman primate model. The observed glucoregulatory and metabolic effects of a partial jejunoileal bypass with this device warrant further investigation to validate the long-term glucometabolic impact of this approach.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Obesidade Mórbida , Animais , Macaca mulatta , Projetos Piloto , Diabetes Mellitus Tipo 2/cirurgia , Obesidade Mórbida/cirurgia , Anastomose Cirúrgica , Fenômenos Magnéticos
14.
Front Surg ; 10: 1253728, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942002

RESUMO

Since the 1970s, magnetic force has been used to augment modern surgical techniques with the aims of minimizing surgical trauma and optimizing minimally-invasive systems. The majority of current clinical applications for magnetic surgery are largely centered around gastrointestinal uses-such as gastrointestinal or bilioenteric anastomosis creation, stricturoplasty, sphincter augmentation, and the guidance of nasoenteric feeding tubes. However, as the field of magnetic surgery continues to advance, the development and clinical implementation of magnetic devices has expanded to treat a variety of non-gastrointestinal disorders including musculoskeletal (pectus excavatum, scoliosis), respiratory (obstructive sleep apnea), cardiovascular (coronary artery stenosis, end-stage renal disease), and genitourinary (stricture, nephrolithiasis) conditions. The purpose of this review is to discuss the current state of innovative magnetic surgical devices under clinical investigation or commercially available for the treatment of non-gastrointestinal disorders.

16.
J Biol Chem ; 299(11): 105325, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37805141

RESUMO

In multicellular organisms, a variety of lipid-protein particles control the systemic flow of triacylglycerides, cholesterol, and fatty acids between cells in different tissues. The chemical modification by oxidation of these particles can trigger pathological responses, mediated by a group of membrane proteins termed scavenger receptors. The lectin-like oxidized low-density lipoprotein (LOX-1) scavenger receptor binds to oxidized low-density lipoprotein (oxLDL) and mediates both signaling and trafficking outcomes. Here, we identified five synthetic proteins termed Affimers from a phage display library, each capable of binding recombinant LOX-1 extracellular (oxLDL-binding) domain with high specificity. These Affimers, based on a phytocystatin scaffold with loop regions of variable sequence, were able to bind to the plasma membrane of HEK293T cells exclusively when human LOX-1 was expressed. Binding and uptake of fluorescently labeled oxLDL by the LOX-1-expressing cell model was inhibited with subnanomolar potency by all 5 Affimers. ERK1/2 activation, stimulated by oxLDL binding to LOX-1, was also significantly inhibited (p < 0.01) by preincubation with LOX-1-specific Affimers, but these Affimers had no direct agonistic effect. Molecular modeling indicated that the LOX-1-specific Affimers bound predominantly via their variable loop regions to the surface of the LOX-1 lectin-like domain that contains a distinctive arrangement of arginine residues previously implicated in oxLDL binding, involving interactions with both subunits of the native, stable scavenger receptor homodimer. These data provide a new class of synthetic tools to probe and potentially modulate the oxLDL/LOX-1 interaction that plays an important role in vascular disease.


Assuntos
Sistema de Sinalização das MAP Quinases , Receptores Depuradores Classe E , Humanos , Receptores Depuradores Classe E/genética , Receptores Depuradores Classe E/química , Receptores Depuradores Classe E/metabolismo , Células HEK293 , Lipoproteínas LDL/metabolismo , Receptores Depuradores/metabolismo , Lectinas/metabolismo
17.
BMC Sports Sci Med Rehabil ; 15(1): 145, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904240

RESUMO

BACKGROUND: Exercise intervention research has shown promising results in preventing and reversing the side effects caused by prostate cancer and its' treatment. However, there are still unanswered questions and the need for additional research. As the field of exercise oncology in the context of prostate cancer presents unique challenges and complexities, seeking the advice of experienced exercise oncology researchers before initiating a similar trial could help to design more effective and efficient studies and help avoid pitfalls. METHODS: A qualitative descriptive study design and a nonprobability, purposive sampling method was employed. An interview guide was developed and included topics such as recruitment, retention, programme goals, research design, health considerations, treatment considerations, adverse events, exercise prescription and outcome tools. Individual semi-structured interviews were conducted and interviews were transcribed and analysed using thematic analysis. RESULTS: Eight individuals with extensive experience working with prostate cancer patients in exercise oncology research settings were interviewed. Four main themes and seven subthemes were generated and supported by the data. Theme 1 highlighted the critical role of recruitment, with associated subthemes on recruitment barriers and recruitment methods. Theme 2 explored the positives and negatives of home-based programmes. Theme 3 focused on specific health characteristics, exercise prescription and outcome measure factors that must be considered when working with prostate cancer cohorts. Finally, theme 4 centered around the emotional dimensions present in exercise oncology trials, relating to both researchers and study participants. CONCLUSION: Exercise oncology remains a challenging area in which to conduct research. Learning from experienced personnel in the field offers valuable information and guidance that could impact the success of future trials.

18.
BMC Med Educ ; 23(1): 746, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817183

RESUMO

BACKGROUND: Primary care has been under-represented in its contribution to the academic literature base on Covid-19 developments. We sought to understand how teaching and learning was modified and developed by primary care academic leaders to support the continuation of primary care-orientated learning during the Covid-19 pandemic; and explore how these changes may shape future educational delivery in primary care. METHODS: We adopted a qualitative approach, using semi-structured interviews of seven General Practice Heads of Teaching (GP HoTs) from UK medical schools. We used mixed deductive and inductive coding to analyse interview transcripts. Modifications and developments were coded to four a priori themes (clinical off-site; clinical on-site; synchronous remote; asynchronous remote). We concurrently used inductive coding to identify developments that did not readily fit into these categories. To understand how participants perceived the developments may shape primary care teaching in the future, we carried out an inductive thematic analysis. RESULTS: A range of modifications and developments were described. Examples of developments include: GP practices being provided with increased flexibility to support ongoing provision of clinical placements (on-site clinical), examples of initiatives enabling students to consult remotely from their homes (off-site clinical), transfer of face-to-face teaching to remote formats (synchronous remote) and development of new, interactive on-line teaching materials (asynchronous remote). One additional theme arose inductively: collaboration and co-operation. For future implications, five themes arose: the evolution of flexible and hybrid clinical placement models; an increased role for telemedicine; increased networking and collaboration; increased active student involvement in patient care; and opportunities for community-based teaching afforded by the pandemic. CONCLUSION: This study highlights how teaching was modified to support the continuation of primary care-based learning during the Covid-19 pandemic, and implications for the future. Collaboration and placement flexibility were notable features in the response. Participants perceived that flexible placement models containing a mixture of clinical on-site with remote synchronous and asynchronous teaching and learning activities, may persist into the post-Covid era. Further research is required to understand which developments become routinely embedded into primary care teaching in the post-Covid era and explain how and why this occurs.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Estudantes , Reino Unido , Atenção Primária à Saúde
19.
Cancer Med ; 12(19): 19394-19405, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37712677

RESUMO

BACKGROUND: Roughly 5% of metastatic cancers present with uncertain origin, for which molecular classification could influence subsequent management; however, prior studies of molecular diagnostic classifiers have reported mixed results with regard to clinical impact. In this retrospective study, we evaluated the utility of a novel molecular diagnostic classifier by assessing theoretical changes in treatment and additional testing recommendations from oncologists before and after the review of classifier predictions. METHODS: We retrospectively analyzed de-identified records from 289 patients with a consensus diagnosis of cancer of uncertain/unknown primary (CUP). Two (or three, if adjudication was required) independent oncologists separately reviewed patient clinical information to determine the course of treatment before they reviewed results from the molecular diagnostic classifier and subsequently evaluated whether the predicted diagnosis would alter their treatment plan. RESULTS: Results from the molecular diagnostic classifier changed the consensus oncologist-reported treatment recommendations for 235 out of 289 patients (81.3%). At the level of individual oncologist reviews (n = 414), 64.7% (n = 268) of treatment recommendations were based on CUP guidelines prior to review of results from the molecular diagnostic classifier. After seeing classifier results, 98.1% (n = 207) of the reviews, where treatment was specified (n = 211), were guided by the tissue of origin-specific guidelines. Overall, 89.9% of the 414 total reviews either expressed strong agreement (n = 242) or agreement (n = 130) that the molecular diagnostic classifier result increased confidence in selecting the most appropriate treatment regimen. CONCLUSIONS: A retrospective review of CUP cases demonstrates that a novel molecular diagnostic classifier could affect treatment in the majority of patients, supporting its clinical utility. Further studies are needed to prospectively evaluate whether the use of molecular diagnostic classifiers improves clinical outcomes in CUP patients.


Assuntos
Segunda Neoplasia Primária , Neoplasias Primárias Desconhecidas , Humanos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/patologia , Estudos Retrospectivos , Patologia Molecular
20.
Patient Prefer Adherence ; 17: 2237-2248, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37706208

RESUMO

Purpose: The evolving treatment landscape in muscle-invasive urothelial carcinoma creates challenges for clinicians and patients in selecting the most appropriate therapy. Here, we aimed to understand adjuvant treatment preferences among patients with muscle-invasive urothelial carcinoma who underwent radical resection, including tradeoffs between efficacy outcomes and toxicity risks. Patients and Methods: An observational, cross-sectional study utilizing a discrete choice experiment was conducted across the United States, United Kingdom, Canada, France, and Germany via a web-based survey. Patients ≥18 years of age who self-reported as having been diagnosed with muscle-invasive urothelial carcinoma were included. Patients indicated their preferences between hypothetical treatment profiles varying in eight attributes relating to efficacy, regimen, and side effects. Preference weights were estimated using hierarchical Bayesian logistic regression; relative attribute importance estimates were calculated. Results: Overall, 207 patients were included (age ≥56 years, 65.7%; male, 54.1%). Patients chose adjuvant treatment 91.2% of the time vs no treatment. Prolonging overall survival from 25 to 78 months was most important, followed by reducing serious side effect risks. Increasing disease-free survival from 12 to 24 months was more important than decreasing risks of fatigue from 54% to 15% and nausea from 53% to 7%. Treatment with the shortest dosing regimen was more important for patients who received neoadjuvant chemotherapy vs patients who did not receive neoadjuvant chemotherapy; prolonging overall survival was more important than reducing the risk of a serious side effect in non-US patients; the opposite was found in the United States. Conclusion: Patients with muscle-invasive urothelial carcinoma who underwent radical resection preferred adjuvant treatment over no treatment regardless of side effects. Patients prioritized overall survival improvements followed by a reduced side effect profile.

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