Circulating tumor cell (CTC) clusters may represent one of the key mechanisms initiating the metastasis process. However, the series of pathophysiologic events by which CTC clusters originate, enter the circulation, and reach the distant sites remain to be identified. The cellular and molecular mechanisms that provide survival advantage for CTC clusters during the transit in the blood stream are also still largely unknown. Understanding the biology of CTC clusters is critical to assess this unified scheme employed by cancer and to device strategies to overcome key pathways responsible for their improved metastatic potential. CTC clusters remain an underdeveloped area of research begging the attention of multidisciplinary cancer research teams. Here, we provide insight on existing preclinical evidence on the potential mechanisms leading to CTC cluster formation and dissemination and on processes that may offer survival advantage. We also offer our perspective on future directions to delineate the role of CTC clusters in metastatic cascade and discuss their clinical significance. .
ObjectivesThe Prediciting factors for response to treatment in carpal tunnel syndrome (PALMS) study is designed to identify prognostic factors for outcome from corticosteroid injection and surgical decompression for carpal tunnel syndrome (CTS) and predictors of cost over 2 years. The aim of this paper is to explore the cross-sectional association of baseline patient-reported and clinical severity with anxiety, depression, health-related quality of life and costs of CTS in patients referred to secondary care.MethodsProspective, multicentre cohort study initiated in 2013. We collected baseline data on patient-reported symptom severity (CTS-6), psychological status (Hospital Anxiety and Depression Scale), hand function (Michigan Hand Questionnaire) comorbidities, EQ-5D-3L (3-level version of EuroQol-5 dimension) and sociodemographic variables. Nerve conduction tests classified patients into five severity grades (mild to very severe). Data were analysed using a general linear model.Results753 patients with CTS provided complete baseline data. Multivariable linear regression adjusting for age, sex, ethnicity, duration of CTS, smoking status, alcohol consumption, employment status, body mass index and comorbidities showed a highly statistically significant relationship between CTS-6 and anxiety, depression and the EQ-5D (p<0.0001 in each case). Likewise, a significant relationship was observed between electrodiagnostic severity and anxiety (p=0.027) but not with depression (p=0.986) or the EQ-5D (p=0.257). National Health Service (NHS) and societal costs in the 3 months prior to enrolment were significantly associated with self-reported severity (p<0.0001) but not with electrodiagnostic severity.ConclusionsPatient-reported symptom severity in CTS is significantly and positively associated with anxiety, depression, health-related quality of life, and NHS and societal costs even when adjusting for age, gender, body mass index, comorbidities, smoking, drinking and occupational status. In contrast, there is little or no evidence of any relationship with objectively derived CTS severity. Future research is needed to understand the impact of approaches and treatments that address psychosocial stressors as well as biomedical factors on relief of symptoms from carpal tunnel syndrome.
Introduction: Gene therapy clinical trials measure steady-state clotting factor expression levels (FELs) to evaluate the modulation of the bleeding phenotype, aiming to offer consistent protection against breakthrough bleeding events. The link between FELs and bleeding risk in people with haemophilia B (PwHB) is not well understood. Aim:We evaluated the association between FEL and ABR in PwHB. Methods:This cross-sectional study extended the CHESS burden of illness studies in Europe and the United States. Recruitment of additional adult males with haemophilia B supplemented the existing CHESS sample size of PwHB and FELs. PwHB receiving prophylaxis were excluded, as fluctuating FELs may have confounded the analysis.Demographic and clinical characteristics were reported descriptively. Any recorded baseline FEL was reported by the haemophilia-treating physicians according to the medical records. Generalised linear models with log link explored the association between changes in FEL and ABR. Results:The study included 407 PwHB and no inhibitors receiving on-demand treatment. Mean age was 36.7 years; 56% from the EU, 44% from the United States. Mean baseline FEL was 9.95 IU/dl (SD, 10.47); mean ABR was 2.4 bleeds/year (SD, 2.64). After adjusting for covariates, the model showed that for every 1% increase in FEL the average ABR decreased by .08 (p < .001). Predicted number of bleeding events according to FEL showed a significant non-linear relationship between FEL and ABR (p < .05). Conclusion:This analysis showed a significant relationship between FEL and ABR, where increases in FEL were associated with decreases in ABR among men with HB in Europe and the US.
One fifth of patients with nonalcoholic fatty liver disease (NAFLD) may progress to nonalcoholic steatohepatitis (NASH), which can increase the risk of cirrhosis, cancer, and death. To date, reported predictors of NASH progression have been heterogeneous. We identified determinants of fibrosis progression in patients with NASH in the United States using physician-reported data from the real-world Global Assessment of the Impact of NASH (GAIN) study, including demographics and clinical characteristics, NASH diagnostic information, fibrosis stage, comorbidities, and treatment. We developed a logistic regression model to assess the likelihood of fibrosis progression since diagnosis, controlling for sociodemographic and clinical variables. An iterative nested model selection approach using likelihood ratio test determined the final model. A total of 989 patients from the GAIN US cohort were included; 46% were women, 58% had biopsy-proven NAFLD, and 74% had fibrosis stage F0–F2 at diagnosis. The final multivariable model included age, years since diagnosis, sex, employment status, smoking status, obesity, fibrosis stage, diagnostic biopsy, Vitamin E, and liver transplant proposed at diagnosis. Odds of progression were 17% higher (odds ratio, 1.17 [95% CI: 1.11–1.23]; P < .001) with each year since NASH diagnosis, 41% lower (0.59 [0.38–0.90]; P = .016) for women than men, 131% higher (2.31 [1.30–4.03]; P = .004) for smokers versus non-smokers, and 89% higher (1.89 [1.26–2.86]; P = .002) with obesity. Odds of progression were also higher with part-time, retired, unemployed, and unable to work due to NASH status versus full-time employment, and when a liver transplant was proposed at diagnosis. Disease duration and severity, obesity, smoking, and lack of full-time employment were significant determinants of fibrosis progression. These findings can support clinical and health-policy decisions to improve NASH management in the US.
Introduction Hemophilia is an inherited disorder that causes a deficiency of a blood clotting factor resulting in a lifelong bleeding diathesis. People with hemophilia (PWH) may experience significant morbidity including potentially life-threatening hemorrhages and accumulation of joint damage and require burdensome and costly chronic treatment with factor replacement therapies. Gene therapies aimed at providing endogenous production of the missing clotting factor have the potential to yield significant health benefits for PWH. Economic evaluation is an important component for the commissioning and funding of new treatments like gene therapies. In economic evaluation, quality-of-life (QoL) is measured using health state utility valuations (HSUV). However, people with inherited and long-term health conditions may adapt to their given health state and adjust their expectations, therefore biasing the estimates of QoL/HSUV (i.e., disease state adaptation (DSA) or "disability paradox"; Albrecht and Devlieger, 1999). Here, we describe the first stages of research to evaluate DSA experienced by PWH. Methods To facilitate the selection of research methodology, a systematic litearure review (SLR) was performed to examine existing studies on QoL/HSUVs for PWH. A SLR was conducted to identify full-text studies by searching electronic databases (e.g. MEDLINE, Web of Science, Cochrane Library). Studies were included in the review using predefined inclusion/exclusion criteria for population, study type, language (English). Additionally, a manual search (last three years) for conferences abstracts was performed to capture the most up-to-date research. Findings from the SLR informed the conceptualisation of a study framework. The proposed research approach was then discussed with an expert panel consisting of clinicians, patient advocacy representatives, and Health Technology Assessment (HTA) specialists. Results The SLR identified 32 studies reporting HSUVs in hemophilia. The studies identified applied a mix of direct and indirect HSUV elicitation techniques. Two studies applied direct time trade-off methodology and the remaining 30 studies adopted indirect valuation methodologies. Utility values were found to vary by disease severity, musculoskeletal damage, bleed frequency, inhibitors, hemophilia subtype, treatment regimen, and adherence. Interestingly, HSUVs derived from valuations from the general public were found to be valued lower than those derived from PWH for the same health states. For example, in Carlsson et al. (2017), general public participants consistently rated significantly lower HSUVs for hemophilia disease states compared to PWH (range: 0.54-0.60 vs. 0.67-0.73), suggesting DSA might exist for PWH. Based on SLR findings, an expert panel discussed the feasibility and acceptability of an approach for conducting a preference elicitation study to directly evaluate DSA in PWH. Preference elicitation is an established research framework that is widely used in health economics. A comparative preference elicitation study was proposed to describe and quantify DSA by comparing responses from PWH, caregivers of PWH, and the general public. Conclusion Based on the SLR and expert panel inputs from clinicians, patients and HTA experts, an agreement was achieved about the research methodology for a new study directly assessing DSA experienced by PWH. Experts agreed that a comparative preference elicitation approach among PWH, caregivers of PWH, and the general public was fit-for-purpose for this research. The impact of DSA on QoL/HSUV should be characterized within economic evaluations of novel treatments with transformative impact on patients' lives, such as gene therapies. Disclosures Martin: HCD Economics: Employment. Mulhern:HCD Economics: Consultancy. Shaikh:HCD Economics: Employment. Asghar:HCD Economics: Employment. O'Hara:HCD Economics: Employment, Equity Ownership. Pedra:HCD Economics: Employment. Sawyer:uniQure Inc.: Employment. Li:uniQure Inc.: Employment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.