The communication of uncertainty in health: A scoping review

ObjectiveTo conduct a scoping review of existing studies that examine communication strategies that address uncertainty in health and categorize them using the taxonomy of uncertainty.MethodsRelevant articles retrieved from ten databases were categorized according to the dimensions of the taxonomy of uncertainty, and study characteristics were extracted from each article.ResultsAll articles (n = 63) explored uncertainty in the context of probabilistic risk and related to scientific issues (n = 63; 100%). The majority focused on complexity (n = 24; 38.1%) and uncertainty experienced by patients (n = 52; 82.5%). Most utilized quantitative methods (n = 46; 73.0%), hypothetical scenarios (n = 49; 77.8%), and focused on cancer (n = 20; 31.7%). Theory guided messages and study design in fewer than half (n = 27; 42.9%).ConclusionsHeterogeneity in terminology used to refer to different types of uncertainties preclude a unified research agenda on uncertainty communication. Research predominately focuses on probability as the source of uncertainty, uncertainties related to scientific issues, and uncertainty experienced by patients.Practice implicationsAdditional efforts are needed to understand providers’ experience of uncertainty, and to identify strategies to address ambiguity. Future studies should use consistent terminology to allow for coherence and advancement of uncertainty communication scholarship. Continued efforts to refine the existing taxonomy should be undertaken.     

The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence

Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAF^V600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer     

A tandem duplication of <Emphasis Type="Italic">BRCA1</Emphasis> exons 1–19 through <Emphasis Type="Italic">DHX8</Emphasis> exon 2 in four families with hereditary breast and ovarian cancer syndrome

Background

Physical activity is inversely associated with the risk of breast cancer among women in the general population. It is not clear whether or not physical activity is associated with the risk of BRCA-associated breast cancer.

Methods

We conducted a case–control study of 443 matched pairs of BRCA mutation carriers to evaluate the association between physical activity and breast cancer risk. Moderate and vigorous physical activities at ages 12–13, ages 14–17, ages 18–22, ages 23–29 and ages 30–34 were determined using the Nurses’ Health Study II Physical Activity Questionnaire. We estimated mean metabolic equivalent task hours/week for moderate, vigorous and total physical activities overall (ages 12–34), during adolescence (ages 12–17) and during early adulthood (ages 18–34). Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for total, moderate and strenuous recreational physical activities and breast cancer risk, by menopausal status.

Results

Overall, there was no significant association between total physical activity and subsequent breast cancer risk (OR_{Q4 vs. Q1} = 1.01, 95% CI 0.69–1.47; P-trend = 0.72). Moderate physical activity between ages 12–17 was associated with a 38% decreased risk of premenopausal breast cancer (OR_{Q4 vs. Q1} = 0.62; 95% CI 0.40–0.96; P-trend = 0.01). We found no association between exercise and breast cancer diagnosed after menopause.

Conclusions

These findings suggest that early-life physical activity is associated with a reduced risk of premenopausal breast cancer among BRCA mutation carriers.

Impact

Future prospective analyses, complemented by mechanistic evidence, are warranted in this high-risk population.

     

Semantic imaging features predict disease progression and survival in glioblastoma multiforme patients

Background

For glioblastoma (GBM), multiple prognostic factors have been identified. Semantic imaging features were shown to be predictive for survival prediction. No similar data have been generated for the prediction of progression. The aim of this study was to assess the predictive value of the semantic visually accessable REMBRANDT [repository for molecular brain neoplasia data] images (VASARI) imaging feature set for progression and survival, and the creation of joint prognostic models in combination with clinical and pathological information.

Methods

189 patients were retrospectively analyzed. Age, Karnofsky performance status, gender, and MGMT promoter methylation and IDH mutation status were assessed. VASARI features were determined on pre- and postoperative MRIs. Predictive potential was assessed with univariate analyses and Kaplan–Meier survival curves. Following variable selection and resampling, multivariate Cox regression models were created. Predictive performance was tested on patient test sets and compared between groups. The frequency of selection for single variables and variable pairs was determined.

Results

For progression free survival (PFS) and overall survival (OS), univariate significant associations were shown for 9 and 10 VASARI features, respectively. Multivariate models yielded concordance indices significantly different from random for the clinical, imaging, combined, and combined?+?MGMT models of 0.657, 0.636, 0.694, and 0.716 for OS, and 0.602, 0.604, 0.633, and 0.643 for PFS. “Multilocality,” “deep white-matter invasion,” “satellites,” and “ependymal invasion” were over proportionally selected for multivariate model generation, underlining their importance.

Conclusions

We demonstrated a predictive value of several qualitative imaging features for progression and survival. The performance of prognostic models was increased by combining clinical, pathological, and imaging features.

     

Treatment-related features improve machine learning prediction of prognosis in soft tissue sarcoma patients

Background and purpose

Current prognostic models for soft tissue sarcoma (STS) patients are solely based on staging information. Treatment-related data have not been included to date. Including such information, however, could help to improve these models.

Materials and methods

A single-center retrospective cohort of 136 STS patients treated with radiotherapy (RT) was analyzed for patients’ characteristics, staging information, and treatment-related data. Therapeutic imaging studies and pathology reports of neoadjuvantly treated patients were analyzed for signs of response. Random forest machine learning-based models were used to predict patients’ death and disease progression at 2 years. Pre-treatment and treatment models were compared.

Results

The prognostic models achieved high performances. Using treatment features improved the overall performance for all three classification types: prediction of death, and of local and systemic progression (area under the receiver operatoring characteristic curve (AUC) of 0.87, 0.88, and 0.84, respectively). Overall, RT-related features, such as the planning target volume and total dose, had preeminent importance for prognostic performance. Therapy response features were selected for prediction of disease progression.

Conclusions

A machine learning-based prognostic model combining known prognostic factors with treatment- and response-related information showed high accuracy for individualized risk assessment. This model could be used for adjustments of follow-up procedures.

     

The sensitivity of the in vitro cytokinesis-blocked micronucleus assay in lymphocytes for different and combined radiation qualities

Purpose

The dose-response relationship and the relative biological effectiveness (RBE) for the induction of micronuclei in lymphocytes was analyzed after irradiation in vitro with a 6-MeV neutron beam that was followed by 240-kV X-rays. The dose range of the combined exposure comprised 1 to 3 Gy. For reference, the dose-effect relationships found after X-ray (0.5 to 5 Gy)-and neutron (0.5 to 4 Gy) exposure applied separately are presented. The possibility of an interaction between the 2 radiation qualities is investigated by the method of isobole calculation termed “envelope of additivity”.

Methods

Micronuclei were analyzed in PHA-stimulated, cytokinesis-blocked human lymphocytes.

Results

The dose-response relationships for the micronucleus frequencies induced by the neutron irradiation, as well as by the mixed exposure, were linear. A saturation effect was indicated after neutron doses higher than 3 Gy. After low LET exposure the dose-response curves were describable by a linear-quadratic model. For neutron-induced micronucleus frequencies, RBE-values of 2 to 3 and for the combined exposure RBE values of 1.5 to 2 were calculated for a range of effect of 0.5 to 1.5 micronuclei/binucleated lymphocyte. No indication was found for an interaction between the damage induced by X-rays and that produced by neutrons under our experimental conditions.

Conclusions

These studies demonstrate a clear dependence of micronucleus induction on radiation quality and empha-size the usefulness of the micronucleus assay in biological dosimetry, also in cases in which high LET radiation or a mixed beam is involved as the radiation source.     

Pseudohypoparathyroidism type I and Albright''s hereditary osteodystrophy with a proximal 15q chromosomal deletion in mother and daughter

A 33-year-old woman and her 71-year-old mother were both found to have pseudohypoparathyroidism type I with Albright's hereditary osteodystrophy associated with a cytogenetic deletion of the proximal part of one chromosome 15, resembling that found in Prader-Willi syndrome. As there are overlapping clinical features between these two syndromes a causal relationship cannot be excluded. However, molecular analyses with 10 probes from this region did not detect any uniparental disomy or deletion, features frequently found in Prader-Willi syndrome.