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| 4. |
- Broman, K. K., et al.
(författare)
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Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy trial II (MSLT-2)
- 2021
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:13, s. 2251-2261
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Tidskriftsartikel (refereegranskat)abstract
- Background For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. Methods In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. Results Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. Conclusions Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.
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| 5. |
- Broman, K. K., et al.
(författare)
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Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis
- 2021
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515. ; 232:4, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown. STUDY DESIGN: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma specific mortality were compared. RESULTS: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86). CONCLUSIONS: SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN. Crown Copyright (C) 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons. All rights reserved.
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- Eroglu, Z., et al.
(författare)
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Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection
- 2022
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Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.
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- Farahi, N, et al.
(författare)
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Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance.
- 2011
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 41:5, s. 673-687
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Tidskriftsartikel (refereegranskat)abstract
- Background Eosinophils are pro-inflammatory cells implicated in the pathogenesis of asthma and atopy. Apoptosis has been proposed as a potential mechanism underlying the resolution of eosinophilic inflammation and studies have indicated the ability of interventions that induce human eosinophil apoptosis to promote the resolution of eosinophilic inflammation. Recently, the cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to enhance neutrophil apoptosis and promote the resolution of neutrophilic inflammation. Objective The purpose of this study was to examine the expression of CDKs in human blood eosinophils, the effects of R-roscovitine on eosinophil survival in vitro and whether R-roscovitine could influence eosinophilic lung inflammation in vivo. Methods Eosinophils were isolated from human peripheral blood and the effects of R-roscovitine on apoptosis, degranulation and phagocytic uptake examined in vitro. The effects of R-roscovitine on eosinophilic lung inflammation in vivo were also assessed using an ovalbumin mouse model. Results Our data demonstrate that human eosinophils express five known targets for R-roscovitine: CDK1, -2, -5, -7 and -9. R-roscovitine induced eosinophil apoptosis in a time- and concentration-dependent manner but also accelerated transition to secondary necrosis as assessed by microscopy, flow cytometry and caspase activation. In addition, we show that R-roscovitine can override the anti-apoptotic signals of GM-CSF and IL-5. We report that the pro-apoptotic effect of R-roscovitine is associated with suppression of Mcl-1L expression and that this compound enhanced phagocytic clearance of eosinophils by macrophages. Finally, we show that R-roscovitine induces apoptosis in murine peripheral blood and spleen-derived eosinophils; despite this, R-roscovitine did not modulate the tissue and lumen eosinophilia characteristic of the ovalbumin mouse model of airway eosinophilia. Conclusion and Clinical Relevance These data demonstrate that R-roscovitine is capable of inducing rapid apoptosis and secondary necrosis in eosinophils but does not affect the onset or improve the resolution of eosinophilic airway inflammation in vivo.
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| 8. |
- Farrow, R., et al.
(författare)
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GO-GN Conceptual Frameworks Guide
- 2021
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- If you’re a doctoral researcher (in any discipline) or someone who produces research in a professional capacity you’ve perhaps encountered the phrase “conceptual framework”. Sometimes a whole chapter of a Ph.D or Ed.D might be given over to investigating the relevance of different frameworks for an area of inquiry, or to synthesizing several frameworks together to ground the approach taken to answering a specific research question. Alternatively, you might not have heard much mention of conceptual frameworks or how they relate to what you are trying to achieve with your research. A conceptual framework brings together a set of ideas and articulates the different concepts that will be used in a study or research project. Because this is highly contextual - and often specific to a particular research question or approach - there aren’t really any general rules that cover how to do this. In addition, there is a lot of ambiguity and impreciseness in the language used to describe this stuff. Sometimes people talk about theoretical frameworks, or models, or a ‘theory of action’ that guides their research project. But do these mean different things? And are there differences between disciplines? In an empirical project the conceptual framework might be used to determine the kinds of questions to ask in a survey, or which data points to collect and focus on. A conceptual framework might be used to generate a hypothesis that is to be tested, or to facilitate the interpretation of results. On the qualitative side a conceptual framework might be used to provide the right kinds of descriptions at different stages of the research process; to identify or explore categories of analysis; or to guide and refine the conclusions drawn by a study. All of these things can happen in a single project! Given the importance and centrality of these frameworks, it might be surprising to learn that relatively little has been written about using them in research. There’s certainly a lot less published about this than research methods or methodology, for instance. (Though different methods often come with specific conceptual frameworks built in or with a more obvious alignment). So, to start making sense of all this we begin by looking at some of the papers that offer systematic guidance or understanding of the role of conceptual frameworks in research. As this guide progresses we’ll bring in perspectives from GO-GN members on their experiences with developing and using conceptual frameworks.
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- Feldman, M, et al.
(författare)
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Community health worker knowledge, attitudes and practices towards COVID-19: Learnings from an online cross-sectional survey using a digital health platform, UpSCALE, in Mozambique
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2, s. e0244924-
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Tidskriftsartikel (refereegranskat)abstract
- Healthcare workers (HCWs) are at the frontline of the Coronavirus Disease 2019 (COVID-19) pandemic response, yet there is a paucity of literature on their knowledge, attitudes and practices (KAP) in relation to the pandemic. Community Health Workers (CHWs) in Mozambique are known locally as agentes polivalentes elementares (APEs). While technical guidance surrounding COVID-19 is available to support APEs, communicating this information has been challenging due to restrictions on travel, face-to-face group meetings and training, imposed from May to August 2020. A digital health platform, upSCALE, that already supports 1,213 APEs and 299 supervisors across three provinces, is being used to support APEs on effective COVID-19 management by delivering COVID-19 sensitive SMS messages, training modules and a COVID-19 KAP survey. The KAP survey, conducted from June 2020 to August 2020, consisted of 10 questions. Of 1,065 active upSCALE APEs, 28% completed the survey. Results indicate that only a small proportion of APEs listed the correct COVID-19 symptoms, transmission routes and appropriate prevention measures (n = (25%), n = (16%) and n = (39%), respectively) specifically included in national health education materials. Misconceptions were mainly related to transmission routes, high risk individuals and asymptomatic patients. 84% said they followed all government prevention guidelines. The results from the KAP survey were used to support the rapid development and deployment of targeted COVID-19 awareness and education materials for the APEs. A follow-up KAP survey is planned for November 2020. Adapting the existing upSCALE platform enabled a better understanding, in real time, of the KAP of APEs around COVID-19 management. Subsequently, supporting delivery of tailored messages and education, vital for ensuring a successful COVID-19 response.
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- Huusko, Johanna M, et al.
(författare)
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Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
- 2018
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency <1%) were analyzed to identify genes and pathways likely to affect SPTB susceptibility. We identified rare, possibly damaging, variants in genes that were common to multiple affected individuals. The glucocorticoid receptor signaling pathway was the most significant (p<1.7e-8) with genes containing these variants in a subgroup of ten Finnish mothers, each having had 2-4 SPTBs. This pathway was replicated among the Danish sister pairs. A gene in this pathway, heat shock protein family A (Hsp70) member 1 like (HSPA1L), contains two likely damaging missense alleles that were found in four different Finnish families. One of the variants (rs34620296) had a higher frequency in cases compared to controls (0.0025 vs. 0.0010, p = 0.002) in a large preterm birth genome-wide association study (GWAS) consisting of mothers of general European ancestry. Sister pairs in replication samples also shared rare, likely damaging HSPA1L variants. Furthermore, in silico analysis predicted an additional phosphorylation site generated by rs34620296 that could potentially affect chaperone activity or HSPA1L protein stability. Finally, in vitro functional experiment showed a link between HSPA1L activity and decidualization. In conclusion, rare, likely damaging, variants in HSPA1L were observed in multiple families with recurrent SPTB.
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| 12. |
- Khan, Sammyh, 1979-, et al.
(författare)
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Making connections : Social identification with new treatment groups for lifestyle management of severe obesity
- 2020
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Ingår i: Clinical Psychology and Psychotherapy. - : John Wiley & Sons. - 1063-3995 .- 1099-0879. ; 27:5, s. 686-696
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Tidskriftsartikel (refereegranskat)abstract
- Groups are regularly used to deliver healthcare services, including the management of obesity, and there is growing evidence that patients' experiences of such groups fundamentally shape treatment effects. This study investigated factors related to patients' shared social identity formed within the context of a treatment group for the management of severe obesity. A cross-sectional survey was administered to patients registered with a UK medical obesity service and enrolled on a group-based education and support programme. Patients (N = 78; M-BMI = 48 on entry to the service) completed measures of group demographics (e.g., group membership continuity) and psychosocial variables (e.g., past experiences of weight discrimination) and reported their social identification with the treatment group. The results showed that patients identified with the treatment group to the extent that there was continuity in membership across the programme and they perceived themselves more centrally in terms of their weight status. Weight centrality was negatively associated with external social support and positively associated with experiences of weight discrimination. Group continuity was positively correlated with session attendance frequency. Patients presenting to clinical treatment services with severe obesity often do so after sustained weight loss failure and exposure to negative societal experiences. This study highlights that providing a treatment environment wherein these experiences can be shared with other patients may provide common ground for development of a new, positive social identity that can structure programme engagement and progression.
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- Tarrant, M., et al.
(författare)
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Patient experiences of a bariatric group programme for managing obesity : A qualitative interview study
- 2017
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Ingår i: British Journal of Health Psychology. - : John Wiley & Sons. - 1359-107X .- 2044-8287. ; 22:1, s. 77-93
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: People with obesity experience a range of physical and psychological ill-health outcomes. This study examined patients' experiences of a group-based programme for the management of morbid obesity delivered within the UK National Health Service. The focus of the study was on the emerging dynamic of the group and patients' perceptions of its impact on health outcomes.Design: A qualitative interview study was conducted and involved patients recruited from a Tier 3 bariatric service in South West England. Verbatim transcripts were analysed using thematic analysis.Methods: Twenty patients (12 females) with a BMI >= 35 kg/m(2) participated in a semi-structured one-to-one interview. Participants had been registered with the bariatric service for at least 6 months. None of the participants had had bariatric surgery.Results: Most participants felt that they had benefited from participating in the group programme and talked about the group as a resource for lifestyle change. Participants' narratives centred on the emergence of a sense of self based upon their participation in the group: establishing psychological connections to other patients, or shared social identity, was regarded as a key mechanism through which the programme's educational material was accessed, and underpinned the experience of social support within the group. Through interaction with other patients, involving the sharing of personal experiences and challenges, participants came to experience their weight ` problem' through a collective lens that they felt empowered them to initiate and sustain individual lifestyle change.Discussion: Bariatric care groups have the potential to support lifestyle change and weight loss and may help address the psychological needs of patients. Nurturing a sense of shared social identity amongst patients with morbid obesity should be a core aim of the care pathway and may provide the foundation for successful translation of dietetic content in group programmes.
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| 16. |
- Khan, Sammyh, 1979-, et al.
(författare)
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Can Raising Awareness about the Psychological Causes of Obesity Reduce Obesity Stigma?
- 2018
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Ingår i: Health Communication. - : Routledge. - 1041-0236 .- 1532-7027. ; 33:5, s. 585-592
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Tidskriftsartikel (refereegranskat)abstract
- Obesity stigma largely remains a socially acceptable bias with harmful outcomes for its victims. While many accounts have been put forward to explain the bias, the role of obesity etiology beliefs has received little scrutiny. The research examined the effect that beliefs about the psychological etiology of obesity have on the expression of obesity stigma and the mechanisms underpinning this effect. Participants (N=463) were asked to evaluate a target person with obesity after reading one of three possible etiologies: psychological, genetic, or behavioral. The presentation of a psychological etiology of obesity elicited less prejudice compared to behavioral causes but greater prejudice compared to genetic causes; observed differences were found to be a function of the agency ascribed to the target's obesity and empathy expressed for the target. The findings highlight the impact that communicating obesity in terms of psychological causes can have for the expression of obesity stigma.
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| 18. |
- Zhang, C., et al.
(författare)
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Measuring fundamental properties in operating solid oxide electrochemical cells by using in situ X-ray photoelectron spectroscopy
- 2010
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Ingår i: Nature Materials. - : Springer Science and Business Media LLC. - 1476-4660 .- 1476-1122. ; 9:11, s. 944-949
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Tidskriftsartikel (refereegranskat)abstract
- Photoelectron spectroscopic measurements have the potential to provide detailed mechanistic insight by resolving chemical states, electrochemically active regions and local potentials or potential losses in operating solid oxide electrochemical cells (SOCs), such as fuel cells. However, high-vacuum requirements have limited X-ray photoelectron spectroscopy (XPS) analysis of electrochemical cells to ex situ investigations. Using a combination of ambient-pressure XPS and CeO2-x/YSZ/Pt single-chamber cells, we carry out in situ spectroscopy to probe oxidation states of all exposed surfaces in operational SOCs at 750 °C in 1 mbar reactant gases H2 and H 2O. Kinetic energy shifts of core-level photoelectron spectra provide a direct measure of the local surface potentials and a basis for calculating local overpotentials across exposed interfaces. The mixed ionic/electronic conducting CeO2-x electrodes undergo Ce3+/Ce4+ oxidation-reduction changes with applied bias. The simultaneous measurements of local surface Ce oxidation states and electric potentials reveal the active ceria regions during H2 electro-oxidation and H2O electrolysis. The active regions extend ∼150 μm from the current collectors and are not limited by the three-phase-boundary interfaces associated with other SOC materials. The persistence of the Ce3+/Ce 4+ shifts in the ∼150 μm active region suggests that the surface reaction kinetics and lateral electron transport on the thin ceria electrodes are co-limiting processes.
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