155155 research outputs found
Sort by
Evolution of Proton Radiotherapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry.
No full textINTRODUCTION
Increasing concern that brainstem toxicity incidence after proton radiotherapy (PRT) might be higher than with photons led to a 2014 XXXX (XX) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the XXXX (XXXX).
METHODS
This prospective multicenter cohort study gathered data from patients under age 22 enrolled on the XXXX, treated between 2002-2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint guidelines by treatment era, histology, and extent of surgical resection.
RESULTS
A total of 467 patients with evaluable PRT plans were reviewed. Median age was 7.1 years (range: <1-21.9), 63.0% (n=296) were male, 76.0% (n=357) were white, and predominant histologies were medulloblastoma (55.0%, n=256) followed by ependymoma (27.0%, n=125). Extent of resection was mainly gross total resection (GTR) (67.0%, n=312), followed by subtotal resection (STR) or biopsy (20.0%, n=92). The XX brainstem constraint metrics most often exceeded were the goal D50% of 52.4 GyRBE (43.3%, n=202) and maximal D50% of 54 GyRBE (12.6%, n=59). The compliance rate increased after the new guidelines (2002-2014: 64.0% vs. 2015-2019: 74.6%, p=0.02), except for ependymoma (46.3% pre vs. 50.0% post guidelines, p=0.86), presenting lower compliance (48.8%) in comparison to medulloblastoma/PNET/pineoblastoma (77.7%), glioma (89.1%), and ATRT (90.9%) (p<0.001). Degree of surgical resection did not affect compliance rates (GTR/NTR 71.0% vs. STR/biopsy 72.8%, p=0.45), even within the ependymoma subset (GTR/NTR 50.5% vs. STR/biopsy 38.1%, p=0.82).
CONCLUSION
Since the publication of the XX guidelines, the pediatric proton community has implemented more conservative brainstem constraints in all patients except those with ependymoma, irrespective of residual disease after surgery. Future work will evaluate if this change in practice is associated with decreased rates of brainstem toxicity
Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.
No full textBACKGROUND
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited.
METHODS
Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed.
RESULTS
Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology.
CONCLUSIONS
In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection
[Case Report: Severe Malnutrition due to Alternative Alimentation in a 6-Month old Infant].
No full textIntegrase strand transfer inhibitor (INSTI) related changes in BMI and risk of diabetes: a prospective study from the RESPOND cohort consortium.
No full textBACKGROUND
With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, this study explored the relationship between INSTI/non-INSTI regimens, BMI changes, and DM risk.
METHODS
RESPOND participants were included if they had CD4, HIV RNA, and ≥ 2 BMI measurements during follow up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥ 11·1 mmol/L, HbA1c ≥ 6·5%/48 mmol/mol, use of antidiabetic medication, or site reported clinical diagnosis. Poisson regression assessed the association between natural log (ln) of time-updated BMI, current INSTI/non-INSTI, and their interactions, on DM risk.
RESULTS
Among 20,865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (IQR 37-52), with a median BMI of 24 kg/m2 (IQR 22-26). There were 785 DM diagnoses with a crude rate of 0·73 (95%CI 0·68-0·78)/100 PYFU. Ln(BMI) was strongly associated with DM (adjusted incidence rate ratio (aIRR) 16·54 per log increase, 95%CI 11·33-24·13; p<0·001). Current INSTI use associated with increased DM risk (IRR 1·58, 95%CI 1·37-1·82; p<0·001) in univariate analyses, only partially attenuated when adjusted for variables including ln(BMI) (aIRR 1·48, 95%CI 1·29-1·71; p<0·001). There was no interaction between ln(BMI), INSTI and non-INSTI use, and DM (p=0·130).
CONCLUSIONS
In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables
Social capital is associated with cooperation and indirect norm enforcement in the field: behavioural evidence from Switzerland
No full textSocial capital, comprising networks, generalized trust, and cooperation norms, is often considered a key factor in promoting prosperity and cooperation. Informal norm enforcement also drives cooperation. While early theories of social capital and norm enforcement propose that networks encourage sanctions, strong reciprocity theory argues that sanctioning non-cooperation is a universal preference. In the lab, people uphold cooperation through sanctions without networks, but this occurs only in regions characterized by high trust levels and strong cooperation norms outside the laboratory. Are trust, cooperation, and enforcement linked in the field, and if so, what are the generative mechanisms? In two neighbourhoods of Bern, one high in social capital and one low, we linked indicators of social capital and expected norm compliance from resident surveys (N = 466) with cooperation, measured with the lost-letter technique (N = 240), and norm enforcement, measured with reactions to transgressions of the antilittering norm (N = 123). Cooperation and indirect enforcement were more prevalent in the high social capital neighbourhood. Direct enforcement was rare in both neighbourhoods. The less optimistic expectations of cooperation and norm compliance prevalent in the low social capital neighbourhood can potentially explain the lower levels of cooperation and norm enforcement
Mapping advanced practice nurses' scope of practice, satisfaction, and drivers of role performance.
No full textBackground: Advanced Practice Nurse (APN) roles in Switzerland include Clinical Nurse Specialist (CNS), Nurse Practitioner (NP) and blended roles. The variety contributes to unclear profiles and scope of practice. Aim: To describe a) the performance of APN tasks according to Hamric's competencies, b) job satisfaction, and c) barriers and facilitators to role performance. Methods: Nationwide cross-sectional survey among clinically working APNs. Inclusion criteria: academic degree, role with advanced nursing competency. Analysis of quantitative and qualitative data using inferential statistics and content analysis. Results: Of the 222 APNs, 49% (n = 108) described themselves as CNSs, 37% (n = 81) as working in a blended role, and 15% (n = 33) as NP. APNs provided the greatest proportion of their tasks in the competency direct clinical practice and the least in ethical decision-making. Group comparisons between roles revealed significant differences in the competencies: direct clinical practice, guidance and coaching, leadership, and evidence-based practice. Job satisfaction was high (76%, n = 165), most often described by the category work content/role (e.g., defined scope of practice). The most frequent barrier to role performance was the category scope of practice (e.g., unclear responsibilities); the most frequent facilitator was the category professional recognition (e.g., respect). Conclusion: The study highlights current APN scope of practice and can support the advancement of the role through clinical practice, educational institutions, and research
Short-term association between air temperature and mortality in seven cities in Norway: A time series analysis.
Full text linkBACKGROUND
The association between ambient air temperature and mortality has not been assessed in Norway. This study aimed to quantify for seven Norwegian cities (Oslo, Bergen, Stavanger, Drammen, Fredrikstad, Trondheim and Tromsø) the non-accidental, cardiovascular and respiratory diseases mortality burden due to non-optimal ambient temperatures.
METHODS
We used a historical daily dataset (1996-2018) to perform city-specific analyses with a distributed lag non-linear model with 14 days of lag, and pooled results in a multivariate meta-regression. We calculated attributable deaths for heat and cold, defined as days with temperatures above and below the city-specific optimum temperature. We further divided temperatures into moderate and extreme using cut-offs at the 1st and 99th percentiles.
RESULTS
We observed that 5.3% (95% confidence interval (CI) 2.0-8.3) of the non-accidental related deaths, 11.8% (95% CI 6.4-16.4) of the cardiovascular and 5.9% (95% CI -4.0 to 14.3) of the respiratory were attributable to non-optimal temperatures. Notable variations were found between cities and subgroups stratified by sex and age. The mortality burden related to cold dominated in all three health outcomes (5.1%, 2.0-8.1, 11.4%, 6.0-15.4, and 5.1%, -5.5 to 13.8 respectively). Heat had a more pronounced effect on the burden of respiratory deaths (0.9%, 0.2-1.0). Extreme cold accounted for 0.2% of non-accidental deaths and 0.3% of cardiovascular and respiratory deaths, while extreme heat contributed to 0.2% of non-accidental and to 0.3% of respiratory deaths.
CONCLUSIONS
Most of the burden could be attributed to the contribution of moderate cold. This evidence has significant implications for enhancing public-health policies to better address health consequences in the Norwegian setting
Characterization of 35 novel NR5A1/SF-1 variants identified in individuals with atypical sexual development: The SF1next study.
Full text linkCONTEXT
Steroidogenic factor 1 (NR5A1/SF-1) is a nuclear receptor that regulates sex development, steroidogenesis and reproduction. Genetic variants in NR5A1/SF-1 are common among differences of sex development (DSD) and associate with a wide range of phenotypes, but their pathogenic mechanisms remain unclear.
OBJECTIVE
Novel, likely disease-causing NR5A1/SF-1 variants from the SF1next cohort of individuals with DSD were characterized to elucidate their pathogenic effect.
METHODS
Different in silico tools were used to predict the impact of novel NR5A1/SF-1 variants on protein function. An extensive literature review was conducted to compare and select the best functional studies for testing the pathogenic effect of the variants in a classic cell culture model. The missense NR5A1/SF-1 variants were tested on the promoter luciferase reporter vector -152CYP11A1_pGL3 in HEK293T cells and assessed for their cytoplasmic/nuclear localization by Western blot.
RESULTS
Thirty-five novel NR5A1/SF-1 variants were identified in the SF1next cohort. Seventeen missense NR5A1/SF-1 variants were functionally tested. Transactivation assays showed reduced activity for 40% of the variants located in the DNA binding domain and variable activity for variants located elsewhere. Translocation assessment revealed three variants (3/17) with affected nuclear translocation. No clear genotype-phenotype, structure-function correlation was found.
CONCLUSIONS
Genetic analyses and functional assays do not explain the observed wide phenotype of individuals with these novel NR5A1/SF-1 variants. In nine individuals, additional likely disease-causing variants in other genes were found, strengthening the hypothesis that the broad phenotype of DSD associated with NR5A1/SF-1 variants may be caused by an oligogenic mechanism
Data sources:
BORIS Portal Bern Open Repository and I...BAF-Online: Proceedings of the Berner Al...HASBonline – Hefte zur Archäologie des M...Informationswissenschaft: Theorie, Metho...Jahrbuch Diakonie SchweizJournal of Eye Movement ResearchJournal of Radiation Oncology Informatic...BOP SerialsVersants. Revista suiza de literaturas r...BORIS ThesesAccess Repository Dashboard
Do you manage Bern Open Repository and Information System (BORIS)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!