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JAMA Network Open Jun 2024Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small... (Observational Study)
Observational Study
IMPORTANCE
Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.
OBJECTIVE
To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.
DESIGN, SETTING, AND PARTICIPANTS
This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.
EXPOSURES
Preoperative chemotherapy (with or without radiotherapy) followed by resection.
MAIN OUTCOMES AND MEASURES
The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.
RESULTS
Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).
CONCLUSIONS AND RELEVANCE
This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
Topics: Humans; Pancreatic Neoplasms; Male; Middle Aged; Female; Adenocarcinoma; Aged; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Cohort Studies; Oxaliplatin; Pancreatectomy
PubMed: 38888920
DOI: 10.1001/jamanetworkopen.2024.17625 -
Frontiers in Public Health 2024Vaccine hesitancy, an important threat to global health, has increased since the onset of the COVID-19 pandemic. The public vaccination of high-profile figures, such as...
INTRODUCTION
Vaccine hesitancy, an important threat to global health, has increased since the onset of the COVID-19 pandemic. The public vaccination of high-profile figures, such as heads of state, has been touted as a potential tool for increasing vaccine acceptance among the general population. However, systematic information on such role modelling is lacking and existing studies focus on a small number of high-income countries. We take advantage of the COVID-19 pandemic to fill this gap.
METHODS
Through a systematic search of internet sources, we first document that most global leaders supported the vaccination campaign and actively communicated their vaccination status to the public. We then turn to a case study to provide experimental evidence on vaccine role modelling for a country in Africa - the region that is most lagging behind in achieving universal immunization coverage. We rely on a randomized survey experiment with 600 citizens in the Democratic Republic of Congo and take advantage of the fact that the Congolese President publicly received a COVID-19 vaccine during the survey period.
RESULTS AND DISCUSSION
Our findings demonstrate that the impact of political leader's role modelling is moderated by trust and depends on media outreach and access. When trust in leaders is lacking, or news on their actions is inaccessible, alternative ambassadors and effective communication methods become crucial in motivating and informing the public. This may be especially relevant in fragile states and remote regions.
Topics: Humans; COVID-19; COVID-19 Vaccines; Democratic Republic of the Congo; Vaccination Hesitancy; Leadership; Female; Male; SARS-CoV-2; Adult; Immunization Programs; Surveys and Questionnaires; Politics; Health Promotion; Vaccination; Middle Aged
PubMed: 38808000
DOI: 10.3389/fpubh.2024.1364927 -
PLoS Biology May 2024Despite significant progress in understanding epigenetic reprogramming of cells, the mechanistic basis of "organ reprogramming" by (epi-)gene-environment interactions...
Despite significant progress in understanding epigenetic reprogramming of cells, the mechanistic basis of "organ reprogramming" by (epi-)gene-environment interactions remained largely obscure. Here, we use the ether-induced haltere-to-wing transformations in Drosophila as a model for epigenetic "reprogramming" at the whole organism level. Our findings support a mechanistic chain of events explaining why and how brief embryonic exposure to ether leads to haltere-to-wing transformations manifested at the larval stage and on. We show that ether interferes with protein integrity in the egg, leading to altered deployment of Hsp90 and widespread repression of Trithorax-mediated establishment of active H3K4me3 chromatin marks throughout the genome. Despite this global reduction, Ubx targets and wing development genes preferentially retain higher levels of H3K4me3 that predispose these genes for later up-regulation in the larval haltere disc, hence the wing-like outcome. Consistent with compromised protein integrity during the exposure, the penetrance of bithorax transformations increases by genetic or chemical reduction of Hsp90 function. Moreover, joint reduction in Hsp90 and trx gene dosage can cause bithorax transformations without exposure to ether, supporting an underlying epistasis between Hsp90 and trx loss-of-functions. These findings implicate environmental disruption of protein integrity at the onset of histone methylation with altered epigenetic regulation of developmental patterning genes. The emerging picture provides a unique example wherein the alleviation of the Hsp90 "capacitor function" by the environment drives a morphogenetic shift towards an ancestral-like body plan. The morphogenetic impact of chaperone response during a major setup of epigenetic patterns may be a general scheme for organ transformation by environmental cues.
Topics: Animals; Drosophila Proteins; Epigenesis, Genetic; Histones; HSP90 Heat-Shock Proteins; Wings, Animal; Drosophila melanogaster; Larva; Gene Expression Regulation, Developmental; Gene-Environment Interaction; Chromosomal Proteins, Non-Histone; Chromatin; Homeodomain Proteins; Epigenetic Memory; Transcription Factors
PubMed: 38805504
DOI: 10.1371/journal.pbio.3002629 -
Appetite May 2024Exercise is associated with changes in food consumption and cognitive function. The aim of this study was to examine the immediate effects of acute exercise on appetite,...
Exercise is associated with changes in food consumption and cognitive function. The aim of this study was to examine the immediate effects of acute exercise on appetite, food choices, and cognitive processes, and the mediating role of cognitive functioning, namely inhibitory control, working memory, cognitive flexibility and decision making. We compared the effects of high-intensity interval exercise (HIIE) to a resting condition on appetite and food choices, using visual analogue rating scales and a computerised portion selection task. Mediation analysis was performed with exercise/rest condition as a predictor variable and cognitive measures were entered as mediating variables and food choice measures as outcomes. Young women with low activity levels, aged between 18 and 35 years with a body mass index (BMI) between 18 and 25 kg/m², were recruited. Participants (n = 30) demonstrated improved performance on a Stroop task following HIIE compared to the rest session, indicating enhanced attentional inhibition. Accuracy on an N-back task was significantly higher after HIIE, indicating an improvement in working memory and response times on the N-back task were shorter after HIIE, suggesting increased processing speed. Delay discounting for food (but not money) was reduced after HIEE but there were no significant effects on go/no-go task performance. On the trail-making task (a measure of cognitive flexibility), the time difference between trail B and A was significantly lower after HIIE, compared to rest. HIIE reduced rated enjoyment and ideal portion size selection for high energy dense foods. The relationship between exercise and food choices was mediated by inhibition as assessed by the Stoop task. These results suggest that HIIE leads to cognitive benefits and a reduced preference for high-calorie foods and that an enhancement of attentional inhibition may underlie this relationship.
PubMed: 38759756
DOI: 10.1016/j.appet.2024.107499 -
Health Science Reports May 2024
PubMed: 38742093
DOI: 10.1002/hsr2.1907 -
International Journal of Medical... Jul 2024Unintended duplicate prescriptions of anticoagulants increase the risk of serious adverse events. Clinical Decision Support Systems (CDSSs) can help prevent such...
BACKGROUND AND OBJECTIVE
Unintended duplicate prescriptions of anticoagulants increase the risk of serious adverse events. Clinical Decision Support Systems (CDSSs) can help prevent such medication errors; however, sophisticated algorithms are needed to avoid alert fatigue. This article describes the steps taken in our hospital to develop a CDSS to prevent anticoagulant duplication (AD).
METHODS
The project was composed of three phases. In phase I, the status quo was established. In phase II, a clinical pharmacist developed an algorithm to detect ADs using daily data exports. In phase III, the algorithm was integrated into the hospital's electronic health record system. Alerts were reviewed by clinical pharmacists before being sent to the prescribing physician. We conducted a retrospective analysis of all three phases to assess the impact of the interventions on the occurrence and duration of ADs. Phase III was analyzed in more detail regarding the acceptance rate, sensitivity, and specificity of the alerts.
RESULTS
We identified 91 ADs in 1581 patients receiving two or more anticoagulants during phase I, 70 ADs in 1692 patients in phase II, and 57 ADs in 1575 patients in phase III. Mean durations of ADs were 1.8, 1.4, and 1.1 calendar days during phases I, II, and III, respectively. In comparison to the baseline in phase I, the relative risk reduction of AD in patients treated with at least two different anticoagulants during phase III was 42% (RR: 0.58, CI: 0.42-0.81). A total of 429 alerts were generated during phase III, many of which were self-limiting, and 186 alerts were sent to the respective prescribing physician. The acceptance rate was high at 97%. We calculated a sensitivity of 87.4% and a specificity of 87.9%.
CONCLUSION
The stepwise development of a CDSS for the detection of AD markedly reduced the frequency and duration of medication errors in our hospital, thereby improving patient safety.
Topics: Decision Support Systems, Clinical; Humans; Anticoagulants; Medication Errors; Algorithms; Medical Order Entry Systems; Retrospective Studies; Electronic Health Records
PubMed: 38669733
DOI: 10.1016/j.ijmedinf.2024.105446 -
Endoscopy Jun 2024Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35 %-60 % in Western countries. We evaluated the real-life...
Effect of optical diagnosis training on recognition and treatment of submucosal invasive colorectal cancer in community hospitals: a prospective multicenter intervention study.
BACKGROUND
Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35 %-60 % in Western countries. We evaluated the real-life effects of training in the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals.
METHODS
In this prospective multicenter study (OPTICAL II), 383 endoscopists from 40 hospitals were invited to follow an e-learning program on the OPTICAL model, to increase sensitivity in detecting T1 CRC in nonpedunculated polyps. Real-life recognition of T1 CRC was then evaluated in 25 hospitals. Endoscopic and pathologic reports of T1 CRCs detected during the next year were collected retrospectively, with endoscopists unaware of this evaluation. Sensitivity for T1 CRC recognition, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists.
RESULTS
1 year after e-learning, 528 nonpedunculated T1 CRCs were recorded for endoscopies performed by 251 endoscopists (118 [47 %] trained). Median T1 CRC size was 20 mm. Lesions were mainly located in the distal colorectum (66 %). Trained endoscopists recognized T1 CRCs more frequently than untrained endoscopists (sensitivity 74 % vs. 62 %; mixed model analysis odds ratio [OR] 2.90, 95 %CI 1.54-5.45). R0 resection rate was higher for T1 CRCs detected by trained endoscopists (69 % vs. 56 %; OR 1.73, 95 %CI 1.03-2.91).
CONCLUSION
Training in optical recognition of T1 CRCs in community hospitals was associated with increased recognition of T1 CRCs, leading to higher en bloc and R0 resection rates. This may be an important step toward more organ-preserving strategies.
PubMed: 38657659
DOI: 10.1055/a-2313-4996 -
Alzheimer's Research & Therapy Apr 2024Neurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in...
BACKGROUND
Neurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in cerebral amyloid angiopathy (CAA), but studies investigating the potential of NFL and GFAP as markers for CAA are lacking. We aimed to investigate NFL and GFAP as biomarkers for neuroaxonal damage and astrocytosis in CAA.
METHODS
For this cross-sectional study serum and cerebrospinal fluid (CSF) samples were collected between 2010 and 2020 from controls, (pre)symptomatic Dutch-type hereditary (D-CAA) mutation-carriers and participants with sporadic CAA (sCAA) from two prospective CAA studies at two University hospitals in the Netherlands. NFL and GFAP levels were measured with Simoa-assays. The association between NFL and GFAP levels and age, cognitive performance (MoCA), CAA-related MRI markers (CAA-CSVD-burden) and Aβ40 and Aβ42 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and ≥55 years to match the specific groups.
RESULTS
We included 187 participants: 28 presymptomatic D-CAA mutation-carriers (mean age 40 years), 29 symptomatic D-CAA participants (mean age 58 years), 59 sCAA participants (mean age 72 years), 33 controls < 55 years (mean age 42 years) and 38 controls ≥ 55 years (mean age 65 years). In presymptomatic D-CAA, only GFAP in CSF (7.7*10pg/mL vs. 4.4*10pg/mL in controls; P<.001) was increased compared to controls. In symptomatic D-CAA, both serum (NFL:26.2pg/mL vs. 12.5pg/mL; P=0.008, GFAP:130.8pg/mL vs. 123.4pg/mL; P=0.027) and CSF (NFL:16.8*10pg/mL vs. 7.8*10pg/mL; P=0.01 and GFAP:11.4*10pg/mL vs. 7.5*10pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only NFL levels were increased compared to controls in both serum (25.6pg/mL vs. 12.5pg/mL; P=0.005) and CSF (20.0*10pg/mL vs 7.8*10pg/mL; P=0.008). All levels correlated with age. Serum NFL correlated with MoCA (P=0.008) and CAA-CSVD score (P<.001). NFL and GFAP in CSF correlated with Aβ42 levels (P=0.01/0.02).
CONCLUSIONS
GFAP level in CSF is an early biomarker for CAA and is increased years before symptom onset. NFL and GFAP levels in serum and CSF are biomarkers for advanced CAA.
Topics: Humans; Neurofilament Proteins; Glial Fibrillary Acidic Protein; Female; Male; Middle Aged; Cross-Sectional Studies; Biomarkers; Aged; Cerebral Amyloid Angiopathy; Amyloid beta-Peptides; Adult; Prospective Studies; Magnetic Resonance Imaging
PubMed: 38654326
DOI: 10.1186/s13195-024-01457-0 -
Cureus Mar 2024Osteoporosis, the silent epidemic, is defined as a systemic skeletal disease characterized by low mineral bone mass and micro-architectural deterioration of bone tissue....
BACKGROUND
Osteoporosis, the silent epidemic, is defined as a systemic skeletal disease characterized by low mineral bone mass and micro-architectural deterioration of bone tissue. Osteoporosis is considered a burden to global economic, social, and health development. Osteoporosis exerts a substantial global influence, markedly influencing rates of illness and death on a broad scale. Clinical features of osteoporosis can include chronic back pain, loss of height, and a stooped posture, as well as an increased risk of fractures in the spine, hip, and wrist. Accurate identification and monitoring of these clinical features are essential for effective management and treatment of osteoporosis. This study aims to identify the knowledge, attitudes, and practices (KAP) of adults (over 18 years) about osteoporosis and identify relations between knowledge, attitudes, and practices with demographic data. Furthermore, to assess the risk factors and preventive measures for osteoporosis.
METHODOLOGY
Data from 446 responders were collected using a Google Forms questionnaire, including questions to assess knowledge, attitudes, and practice levels among adults 18 years and above in the United Arab Emirates (UAE). The collected data and statistical analysis were done through the IBM® SPSS® Statistics. Chi-Square was used in SPSS Statistics; the chi-square test was used for the relation between categorical variables, and P less than 0.05 was the cut-off level of significance.
RESULTS
The research revealed that 41.9% of the participants had good knowledge, 38.8% had a positive attitude, and 45.3% had poor practices. The results also showed that there is a statistically significant correlation between gender and knowledge, attitudes, and practices.
CONCLUSION
Our research demonstrates that there's a statistically significant correlation between gender variables with knowledge, attitudes, and practices. These findings have important implications in assessing the correlation between variables in our research that could be used to prevent osteoporosis further, target the specific demographic group, and provide the required education. Overall, our research contributes to a better understanding of the knowledge, attitude, and practices towards Osteoporosis among adults in the UAE and underscores the importance of further awareness in this area.
PubMed: 38618442
DOI: 10.7759/cureus.56084 -
Journal of Clinical Medicine Apr 2024Implementing innovations emerging from clinical research can be challenging. Thermal imagers provide an accessible diagnostic tool to increase the accuracy of burn...
Implementing innovations emerging from clinical research can be challenging. Thermal imagers provide an accessible diagnostic tool to increase the accuracy of burn wound depth assessment. This mixed-methods implementation study aimed to assess the barriers and facilitators, design implementation strategies, and guide the implementation process of thermal imaging in the outpatient clinic of a burn centre. This study was conducted between September 2022 and February 2023 in Beverwijk, The Netherlands. Semi-structured interviews with burn physicians guided by the Consolidated Framework for Implementation Research (CFIR) were conducted to identify barriers and facilitators. Based on the barriers, implementation strategies were developed with the CFIR-ERIC Matching Tool, and disseminated to support the uptake of the thermal imager. Subsequently, thermal imaging was implemented in daily practice, and an iterative RE-AIM approach was used to evaluate the implementation process. Common facilitators for the implementation of the thermal imager were the low complexity, the relative advantage above other diagnostic tools, and benefits for patients. Common barriers were physicians' attitude towards and perceived value of the intervention, the low compatibility with the current workflow, and a lack of knowledge about existing evidence. Six implementation strategies were developed: creating a formal implementation blueprint, promoting adaptability, developing educational materials, facilitation, conducting ongoing training, and identifying early adopters. These strategies resulted in the effective implementation of the thermal imager, reflected by a >70% among eligible patients, and >80% and . Throughout the implementation process, compatibility, and available resources remained barriers, resulting in low ratings on RE-AIM dimensions. This study developed implementation strategies based on the identified CFIR constructs that impacted the implementation of a thermal imager for burn wound assessment in our outpatient clinic. The experiences and findings of this study could be leveraged to guide the implementation of thermal imaging and other innovations in burn care.
PubMed: 38610828
DOI: 10.3390/jcm13072061