Adaptively triggered comparisons enhance perceptual category learning: evidence from face learning.

Categorical learning is important and often challenging in both specialized domains, such as medical image interpretation, and commonplace ones, such as face recognition. Research has shown that comparing items from different categories can enhance the learning of perceptual classifications, particularly when those categories appear highly similar. Here, we developed and tested novel adaptively triggered comparisons (ATCs), in which errors produced during interactive learning dynamically prompted the presentation of active comparison trials. In a facial identity paradigm, undergraduate participants learned to recognize and name varying views of 22 unknown people. In Experiment 1, single-item classification trials were compared to a condition in which ATC trials were generated whenever a participant repeatedly confused two faces. Comparison trials required discrimination between simultaneously presented exemplars from the confused categories. In Experiment 2, an ATC condition was compared to a non-adaptive comparison condition. Participants learned to accuracy and speed criteria, and completed immediate and delayed posttests. ATCs substantially enhanced learning efficiency in both experiments. These studies, using a novel adaptive procedure guided by each learner's performance, show that adaptively triggered comparisons improve category learning.

Multiple expressions of "expert" abnormality gist in novices following perceptual learning.

With a brief half-second presentation, a medical expert can determine at above chance levels whether a medical scan she sees is abnormal based on a first impression arising from an initial global image process, termed "gist." The nature of gist processing is debated but this debate stems from results in medical experts who have years of perceptual experience. The aim of the present study was to determine if gist processing for medical images occurs in naïve (non-medically trained) participants who received a brief perceptual training and to tease apart the nature of that gist signal. We trained 20 naïve participants on a brief perceptual-adaptive training of histology images. After training, naïve observers were able to obtain abnormality detection and abnormality categorization above chance, from a brief 500 ms masked presentation of a histology image, hence showing "gist." The global signal demonstrated in perceptually trained naïve participants demonstrated multiple dissociable components, with some of these components relating to how rapidly naïve participants learned a normal template during perceptual learning. We suggest that multiple gist signals are present when experts view medical images derived from the tens of thousands of images that they are exposed to throughout their training and careers. We also suggest that a directed learning of a normal template may produce better abnormality detection and identification in radiologists and pathologists.

Connecting Adaptive Perceptual Learning and Signal Detection Theory in Skin Cancer Screening.

Combining perceptual learning techniques with adaptive learning algorithms has been shown to accelerate the development of expertise in medical and STEM learning domains (Kellman & Massey, 2013; Kellman, Jacoby, Massey & Krasne, 2022). Virtually all adaptive learning systems have relied on simple accuracy data that does not take into account response bias, a problem that may be especially consequential in multi-category perceptual classifications. We investigated whether adaptive perceptual learning in skin cancer screening can be enhanced by incorporating signal detection theory (SDT) methods that separate sensitivity from criterion. SDT-style concepts were used to alter sequencing, and separately to define mastery (category retirement). SDT retirement used a running d' estimate calculated from a recent window of trials based on hit and false alarm rates. Undergraduate participants used a Skin Cancer PALM (perceptual adaptive learning module) to learn classification of 10 cancerous and readily-confused non-cancerous skin lesion types. Four adaptive conditions varied either the type of adaptive sequencing (standard vs. SDT) or retirement criteria (standard vs. SDT). A non-adaptive control condition presented didactic instruction on dermatologic screening in video form, including images, classification schemes, and detailed explanations. All adaptive conditions robustly outperformed the non-adaptive control in both learning efficiency and fluency (large effect sizes). Between adaptive conditions, SDT retirement criteria produced greater learning efficiency than standard, accuracy-based mastery criteria at both immediate and delayed posttests (medium effect sizes). SDT sequencing and standard adaptive sequencing did not differ. SDT enhancements to adaptive perceptual learning procedures have potential to enhance learning efficiency.

Comparisons in Adaptive Perceptual Category Learning.

Recent work suggests that learning perceptual classifications can be enhanced by combining single item classifications with adaptive comparisons triggered by each learner's confusions. Here, we asked whether learning might work equally well using all comparison trials. In a face identification paradigm, we tested single item classifications, paired comparisons, and dual instance classifications that resembled comparisons but required two identification responses. In initial results, the comparisons condition showed evidence of greater efficiency (learning gain divided by trials or time invested). We suspected that this effect may have been driven by easier attainment of mastery criteria in the comparisons condition, and a negatively accelerated learning curve. To test this idea, we fit learning curves and found data consistent with the same underlying learning rate in all conditions. These results suggest that paired comparison trials may be as effective in driving learning of multiple perceptual classifications as more demanding single item classifications.

Developing an Education Pathway for Breast Cancer Patients Receiving Rapid Diagnostic Testing: Investigating Informational and Supportive Care Needs.

Several studies have examined the informational needs of patients undergoing the breast diagnostic process where needs are highest during testing and prior to receiving a diagnosis. To aid in the development of an education pathway, we identified patient information needs. A multi-method approach to identify areas of need and to understand when and how information should be provided to patients was undertaken. The methods included an environmental scan of consumer health information, ethnographic observation of the patient clinical experience, key informant interviews, and a needs assessment survey. The data collected from the environmental scan, ethnography, and interviews were used to develop the items in the survey. The survey was developed around four domains: (1) Medical Procedures and Tests, (2) Understanding the Rapid Diagnostic Process, (3) Breast Cancer and Other Breast Conditions, and (4) Support and Coping. A total of 101 patients completed the survey. Mean importance scores were significantly different between domains of information need (p < .0001) and significantly higher for the 'Medical Procedures and Tests' domain compared with all others. Multivariate analysis suggested that participants with higher levels of education (p = .02) and a preference to speak English at home (p = .009) tended to rate the importance of 'Support and Coping' information lower than other participants. Information about medical procedures and tests are most important for the patients undergoing rapid diagnostic testing in our sample. Education materials that are tailored to patient needs should be provided to patients during this stage of the cancer journey to help meet informational needs.

Comparing Adaptive and Random Spacing Schedules during Learning to Mastery Criteria.

Adaptive generation of spacing intervals in learning using response times improves learning relative to both adaptive systems that do not use response times and fixed spacing schemes (Mettler, Massey & Kellman, 2016). Studies have often used limited presentations (e.g., 4) of each learning item. Does adaptive practice benefit learning if items are presented until attainment of objective mastery criteria? Does it matter if mastered items drop out of the active learning set? We compared adaptive and non-adaptive spacing under conditions of mastery and dropout. Experiment 1 compared random presentation order with no dropout to adaptive spacing and mastery using the ARTS (Adaptive Response-time-based Sequencing) system. Adaptive spacing produced better retention than random presentation. Experiment 2 showed clear learning advantages for adaptive spacing compared to random schedules that also included dropout. Adaptive spacing performs better than random schedules of practice, including when learning proceeds to mastery and items drop out when mastered.

Adaptive vs. Fixed Spacing of Learning Items: Evidence from Studies of Learning and Transfer in Chemistry Education.

Spacing presentations of learning items across time improves memory relative to massed schedules of practice - the well-known spacing effect. Spaced practice can be further enhanced by adaptively scheduling the presentation of learning items to deliver customized spacing intervals for individual items and learners. ARTS - Adaptive Response-time-based Sequencing (Mettler, Massey, & Kellman 2016) determines spacing dynamically in relation to each learner's ongoing speed and accuracy in interactive learning trials. We demonstrate the effectiveness of ARTS when applied to chemistry nomenclature in community college chemistry courses by comparing adaptive schedules to fixed schedules consisting of continuously expanding spacing intervals. Adaptive spacing enhanced the efficiency and durability of learning, with learning gains persisting after a two-week delay and generalizing to a standardized assessment of chemistry knowledge after 2-3 months. Two additional experiments confirmed and extended these results in both laboratory and community college settings.

Informational needs of brain metastases patients and their caregivers.

BACKGROUND: In response to a dearth of formal health information targeted towards patients with brain metastases and their caregivers, a formal informational and supportive care needs assessment was conducted. METHODS: Brain metastases patients and caregivers who attended a clinic focused on the treatment of brain metastases at a tertiary medical center completed a self-report survey to assess informational needs across 6 domains: medical, physical, practical, social, emotional, and spiritual informational needs. Univariate and multivariate analyses of associations between variables was conducted using linear regression models. RESULTS: A total of 109 patients and 77 caregivers participated. Patients and caregivers both prioritized medical and physical informational domains, with a large focus on symptoms and side-effect profiles, significance of brain metastases locations and their implications, available treatment options and their risks and benefits, prognoses and follow-ups if treatment is completed, and end-of-life experiences and supports. One-on-one counseling was preferred by both caregivers and patients for these domains, as well as for practical informational needs; while patients preferred pamphlets to address social, emotional and spiritual informational needs, caregivers preferred one-on-one counseling for the former two domains as well. CONCLUSIONS: Brain metastases patients and their caregivers prioritize medical and physical informational needs, with one-on-one counseling and pamphlets being the most preferred modalities for information provision. Further exploration regarding existing non-validated resources and the development of tailored resources to address the unique needs of these patient and caregiver populations are warranted.

Correlation of differential ascites volume with primary cytoreductive surgery outcome, lymph node involvement, and disease recurrence in advanced ovarian cancer.

OBJECTIVE: High-grade serous ovarian cancer accounts for a disproportionate number of deaths from gynecologic malignancies. It typically presents at an advanced stage and with a high volume of ascites a common presenting feature. The aims of this study is to evaluate the association between ascites volume at the time of primary surgery for advanced stage ovarian cancer with surgical outcomes and patterns of recurrence. METHODS: A retrospective review of stage III/IV high-grade serous ovarian cancer patients who underwent primary surgery at two centers between March 2003 to June 2016. Patients were categorized as low-volume ascites (≤ 200 mL) vs high-volume (≥ 1 L). Patients with an unknown volume of ascites or neoadjuvant chemotherapy were excluded. Patients' characteristics were compared for the two groups. Probability of recurrence over time and the HR from a proportional hazards model for sub-distribution were calculated. RESULTS: A total of 210 patients were included, 90 (42.9%) patients in the low-volume and 120 (57.1%) patients in the high-volume group. Patients in the low-volume group were older with a median age of 60.2 years vs 56.8 years in the high-volume group and had lower serum CA-125 levels (mean 223 vs 971.5 U/mL). The low-volume group had better surgical outcome with suboptimal debulking (> 1 cm residual disease) in only 17.8 % vs 39.2 % in the high-volume group and had longer median time to recurrence (2.8 years in low-volume vs 1.6 years high-volume group). At the time of recurrence, the low-volume group had a less disseminated pattern of recurrence, lower rates of ascites (20 % in the low-volume group vs 37.2 % in the high-volume group), and a trend toward lower serum CA125 levels (mean 352.8 vs 596.9 U/mL). CONCLUSIONS: Advanced stage serous ovarian cancer patients who present with low-volume ascites have lower serum CA125 levels, more optimal cytoreduction rates, and longer disease-free interval. The low-volume group had less ascites, less disseminated disease, and a trend toward lower serum CA125 levels at the time of recurrence.

The Synergy of Passive and Active Learning Modes in Adaptive Perceptual Learning.

Adaptive learning systems that generate spacing intervals based on learner performance enhance learning efficiency and retention (Mettler, Massey & Kellman, 2016). Recent research in factual learning suggests that initial blocks of passive trials, where learners observe correct answers without overtly responding, produce greater learning than passive or active trials alone (Mettler, Massey, Burke, Garrigan & Kellman, 2018). Here we tested whether this passive + active advantage generalizes beyond factual learning to perceptual learning. Participants studied and classified images of butterfly genera using either: 1) Passive Only presentations, 2) Passive Initial Blocks followed by active, adaptive scheduling, 3) Passive Initial Category Exemplar followed by active, adaptive scheduling, or 4) Active Only learning. We found an advantage for combinations of active and passive presentations over Passive Only or Active Only presentations. Passive trials presented in initial blocks showed the best performance, paralleling earlier findings in factual learning. Combining active and passive learning produces greater learning gains than either alone, and these effects occur for diverse forms of learning, including perceptual learning.

A prospective study of patient-centred outcomes in the management of malignant pleural effusions.

BACKGROUND: In a patient population with a limited life expectancy, malignant pleural effusion can significantly impact quality of life (QoL). Different treatment options are available, each with its own effect on QoL. To date, satisfaction with treatment options has not been evaluated. PURPOSE: To evaluate QoL and satisfaction with treatment using patient-reported outcomes for four different treatment strategies. DESIGN: A prospective, cohort study that compared four treatment options: indwelling pleural catheter (IPC); video assisted thoracic surgery (VATS) and IPC; chest tube and talc slurry; and VATS talc poudrage. SETTING: A total of 104 participants were treated across four acute care teaching hospitals in a large Canadian city. MEASUREMENTS: Patient-reported outcomes were assessed using functional assessment of chronic illness therapy-palliative (FACIT-PAL), London Chest Activity of Daily Living scale and FACIT-treatment satisfaction questionnaires. RESULTS: No significant difference was identified between the four treatments based on patient-reported outcomes. VATS talc poudrage provided the most durable improvement. At the 6-week post-treatment time point, the highest patient satisfaction was noted in patients who received VATS and talc pleurodesis, lowest satisfaction in patients with chest tube and talc pleurodesis; however, the differences were not statistically significant (p=0.20). VATS and talc pleurodesis had the highest scores at 6 weeks for recommendation of treatment to others; however, the comparison with other treatment groups was not statistically significant (p=0.22). For FACIT-PAL, total scores when analysed as one group, there was a statistically significant increasing trend (indicating improvement) (p<0.0001). Breathlessness, measured using the London Chest Activity of Daily Living scale, indicated a statistically decreasing trend, suggesting an improvement (p=0.0003). There was no statistically significant difference in trends over time between the four treatment groups. CONCLUSIONS: While all treatment options addressed the patients' symptoms and relieved dyspnoea, an IPC offered effective treatment with minimal discomfort and time in hospital yet still high satisfaction.

A comparison of adaptive and fixed schedules of practice.

Understanding and optimizing spacing during learning is a central topic for research in learning and memory and has substantial implications for real-world learning. Spacing memory retrievals across time improves memory relative to massed practice-the well-known spacing effect. Most spacing research has utilized fixed (predetermined) spacing intervals. Some findings indicate advantages of expanding over equal spacing (e.g., Landauer & Bjork, 1978); however, evidence is mixed (e.g., Karpicke & Roediger, 2007), and the field has lacked an integrated explanation. Learning may instead depend on interactions of spacing with an underlying variable of learning strength that varies for learners and items, and it may be better optimized by adaptive adjustments of spacing to learners' ongoing performance. Two studies investigated an adaptive spacing algorithm, Adaptive Response-Time-based Sequencing or ARTS (Mettler, Massey & Kellman, 2011) that uses response-time and accuracy to generate spacing. Experiment 1 compared adaptive scheduling with fixed schedules having either expanding or equal spacing. Experiment 2 compared adaptive schedules to 2 fixed "yoked" schedules that were copied from adaptive participants, equating average spacing across conditions. In both experiments, adaptive scheduling outperformed fixed conditions at immediate and delayed tests of retention. No evidence was found for differences between expanding and equal spacing. Yoked conditions showed that learning gains were due to adaptation to individual items and learners. Adaptive spacing based on ongoing assessments of learning strength yields greater learning gains than fixed schedules, a finding that helps to understand the spacing effect theoretically and has direct applications for enhancing learning in many domains. (PsycINFO Database Record

Illness intrusiveness and subjective well-being in patients with glioblastoma.

Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on quality of life (QOL) is poorly understood. In other patient populations, illness intrusiveness (the extent to which disease and treatment disrupts valued activities and interests) is associated with low subjective well-being, after controlling for disease and treatment variables. In this cross-sectional cohort study, we examined the relations among illness intrusiveness, disease burden, and subjective well-being in GBM. 73 GBM patients completed validated self-report measures of depression, positive affect, illness intrusiveness, and health-related QOL. Responses were compared to data from six other cancer groups using repeated measures analyses of variance. Hierarchical multiple-regression analyses tested the hypothesis that illness intrusiveness accounts for well-being after controlling for the effects of disease burden. GBM patients reported less positive affect, more depression, and more illness intrusiveness than people with other cancers. Illness intrusiveness correlated with depression and (low) positive affect. Associations among cancer symptoms, depression, and positive affect decreased when illness intrusiveness was added to regression equations. Good performance status and high cancer-symptom burden were associated with illness intrusiveness and depression. GBM patients report greater distress, lower positive affect, and more illness intrusiveness than people with other cancers. Subjective well-being is mediated in part by illness intrusiveness in this population. In addition to medical treatment, efforts to help patients remain engaged in valued activities and interests may help preserve QOL after the diagnosis of a GBM.

Accumulated Delivered Dose Response of Stereotactic Body Radiation Therapy for Liver Metastases.

PURPOSE: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases. METHODS AND MATERIALS: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board-approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm(3) (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm(3) gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping. RESULTS: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose-response predictor than the minPTV dose. CONCLUSIONS: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose-response outcomes should increase the concordance between the planned and delivered doses.

Neoadjuvant chemoradiation and surgery improves survival outcomes compared with definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung cancer.

OBJECTIVES: The objective of this study was to compare survival in patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT) or surgery plus neoadjuvant chemoradiation or chemotherapy (CRTS). METHODS: A retrospective analysis of 242 patients with stage IIIA (N2) NSCLC treated with curative intent between 1997 and 2007, identified 215 patients with surgically resectable disease. Overall survival outcomes were analysed using the Kaplan-Meier plots, log-rank tests and Cox proportional hazards models adjusting for age, gender, histology, smoking history and performance status. Recurrences were compared using competing risks methods, including the proportional subdistribution hazards regression model. RESULTS: CRTS was used to treat 104 patients and CRT in 111. Comparing CRTS with CRT patients, median age was 60 vs 62, 50 (48%) vs 69 (62%) were male and 65 (62.5%) vs 60 (54%) had adenocarcinoma. Of CRTS patients, 83 (80%) had a lobectomy. CRTS patients compared with CRT patients had decreased risk of recurrence at any site [hazard ratio (HR) = 0. 46, 95% confidence interval (CI): 0.32-0.64 P < 0.0001], local recurrence (HR = 0.50, 95% CI: 0.29-0.87, P = 0.013), loco--regional recurrence (HR = 0.51, 95% CI: 0.33-0.78, P = 0.002) and death (HR: 0.45, 95% CI: 0.33-0.62, P < 0.0001) with a median survival of 4.2 years vs 1.7 years). Risk of distant recurrence was also reduced in the surgical group (HR: 0.57; 95% CI: 0.38-0.87, P = 0.017). Treatment-related mortality was low in both cohorts. CONCLUSION: For patients with surgically resectable stage IIIA (N2) NSCLC, neoadjuvant therapy plus surgery reduces loco-regional and distant recurrence and improves survival. Treatment-related mortality was not significantly increased compared with the patients treated with CRT alone.

Performance characteristics of a brief Family History Questionnaire to screen for Lynch syndrome in women with newly diagnosed endometrial cancer.

OBJECTIVE: The brief Family History Questionnaire (bFHQ) was developed to identify endometrial cancer patients whose family histories suggest Lynch syndrome (LS). We compared the bFHQ, extended Family History Questionnaire (eFHQ) and dictated medical records (DMRs) to determine which family history screening strategy is superior in identifying LS in unselected women with newly diagnosed endometrial cancer that have undergone universal germline testing. METHODS: Prospective cohort study recruited women with newly diagnosed endometrial cancer to evaluate screening strategies to identify LS. Participants completed bFHQ and eFHQ, had tumor assessed with immunohistochemistry (IHC) for mismatch repair proteins (MMR) and micro-satellite instability testing and underwent universal germline testing for LS. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) were compared between the family history screening strategies as well as IHC. RESULTS: 118 of 182 eligible patients (65%) consented; 87 patients (74%) were evaluable with both family history and germline mutation status. Median age was 61years (range 26-91). All 7 patients with confirmed LS were correctly identified by bFHQ, compared to 5 and 4 by eFHQ and DMR, respectively. The sensitivity, specificity, PPV and NPV values of bFHQ were 100%, 76.5%, 25.9% and 100%, respectively, performing similar to IHC testing. While eFHQ was more specific than bFHQ (86.7% vs. 76.5%, P=0.007), 2 cases of LS were missed. CONCLUSIONS: The patient-administered bFHQ effectively identified women with confirmed LS and is a good screening tool to triage women with endometrial cancer for further genetic assessment.

Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing.

BACKGROUND: Immunohistochemistry (IHC) for mismatch repair protein expression, microsatellite instability (MSI) testing, tumor morphology, and family history were compared to determine which screening strategy is superior in identifying Lynch syndrome (LS) in unselected women with newly diagnosed endometrial cancer (EC) who have undergone universal germline mutation testing. METHODS: A prospective cohort study was performed that recruited women with newly diagnosed EC. Participants completed a family history assessment with molecular characterization of EC with IHC and MSI testing and EC assessment for LS-associated morphologic features and underwent universal germline mutation testing for mutations in the mismatch repair pathway. The sensitivity, specificity, and positive and negative predictive values were compared between the screening strategies. RESULTS: A total of 118 (65%) of 182 consecutive women with EC participated. Of these, 34 women (29%) had tumors that were IHC deficient and 27 women (23%; N = 117) had tumors that were positive for MSI. Twenty women (17%) met IHC criteria and 16 women (15.2%, N = 105) met family history criteria based on Ontario Ministry of Health Criteria for the genetic assessment for LS. Seven women (5.9%) had a germline mutation: 4 had MLH1 (mutL homolog 1), 2 had MSH6 (mutS homolog 6), and 1 had MSH2 (mutS homolog 2). IHC in women aged <60 years had the best performance characteristics, with a sensitivity of 100%, a specificity of 86.1%, a positive predictive value of 58.3%, and a negative predictive value of 100%. Family history and tumor morphology both had the lowest sensitivity at 71.4%. Overall tumor morphology had the poorest performance, with a specificity of 42.1%. CONCLUSIONS: The mutation rate of 5.9% was higher than expected in this unselected cohort of women with EC. The superior screening strategy to identify women presenting with EC is universal IHC screening in women aged <60 years.

Glioblastoma treatment in the elderly in the temozolomide therapy era.

BACKGROUND: optimal treatment of glioblastoma (gBM) in the elderly remains unclear. the impact of age on treatment planning, toxicity, and efficacy at a Canadian Cancer Centre was retrospectively reviewed. METHODS: glioblastoma patients treated consecutively between 2004 and 2008 were reviewed. utilizing 70 years as the threshold for definition of an elderly patient, treatments and outcome were compared in younger and elderly populations. RESULTS: four hundred and twenty one patients were included in this analysis and median overall survival (oS) for the entire cohort was 9.8 months. 290 patients were aged <70 (median age 57, range 17- 69) and 131 were aged ≥ 70 (median age 76, range 70-93). patients ≥ 70 were more likely to receive best supportive care (BSC) and all patients >70 who were treated with radiotherapy received <60 gy (P<0.001), except one. patients aged >70 demonstrated inferior survival (one year oS 16% versus 54% for those <70, hr 3.46, P<0.001). in patients treated with BSC only, age had no impact on survival (median survival two months in both groups, hr 0.89, P=0.75). for those treated with higher doses of radiotherapy (>30 gy to <60 gy), one year survival was 19% versus 24% in patients aged >70 versus <70 (hr 1.47, P=0.02) respectively. CONCLUSION: in this retrospective single institution series, elderly patients were more likely to be treated with BSC or palliative doses of radiotherapy. randomized phase iii study results are required for guidance in treatment of this population of patients.

Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin.

OBJECTIVE: Oral progestin is an alternative to hysterectomy for women with complex atypical hyperplasia (CAH) or grade one endometrial cancer (G1EC) who wish fertility preservation. We evaluated treatment efficacy and fertility outcomes in this population. METHODS: Women <45 y treated with oral progestin for CAH or G1EC were identified from two cancer centers. Data were obtained from medical records and telephone questionnaires. Time until complete response (CR), and from CR until recurrence was censored for patients without events and analyzed for associations with patient and treatment characteristics; cumulative incidence functions were used to estimate event probability over time. RESULTS: 44 patients were identified, 19 (43%) with CAH and 25 (57%) with G1EC. Median age was 36.5 y (26-44). 24 (55%) achieved CR (median time: 5.7 months). Older age was associated with a lower likelihood of CR (HR 0.84, p=0.0003, 95% CI, 0.8-0.9). CR probability appeared to plateau after 12 months of therapy. Among those with CR, 13 (54%) recurred (median time 3.5 y). 24 patients (55%) underwent hysterectomy; 3 (13%) were upstaged. 11 (25%) underwent fertility treatment with the following outcomes: 6 (55%) no pregnancy, 2 (18%) at least one live infant, and 3 (27%) spontaneous abortion. One achieved a live birth without intervention. CONCLUSION: Oral progestin is an effective temporizing fertility-sparing treatment for women with CAH/G1EC. Fertility specialist involvement is recommended due to the low live birth rate without intervention. Progestin therapy should be re-evaluated at 1 year in non-responders due to a low probability of success. Hysterectomy is recommended after childbearing due to a high recurrence rate.

Malignant hyperthermia in Canada: characteristics of index anesthetics in 129 malignant hyperthermia susceptible probands.

BACKGROUND: Between 1992 and 2011, 373 Canadian individuals with adverse anesthetic reaction were referred to the Malignant Hyperthermia Unit in Toronto, Ontario, Canada for malignant hyperthermia (MH) diagnostic testing. We analyzed the epidemiologic characteristics of the index adverse anesthetics for those probands who were confirmed to be MH susceptible. METHODS: One hundred twenty-nine proband survivors of adverse anesthetic reactions, whose MH susceptible status was confirmed by caffeine-halothane contracture testing were selected. Individuals were excluded if the index anesthetic record was not available for review. Data regarding demographics, clinical signs, laboratory findings, treatment, and complications were retrospectively compiled and analyzed. A Fisher exact test and χ test were applied to compare categorical variables. The Wilcoxon rank-sum test was applied with continuous variables. RESULTS: Young males (61.2%) dominated among selected patients. Seventeen of 129 (13.2%) patients had prior unremarkable anesthesia. Anesthetic triggers were volatile-only (n = 58), succinylcholine-only (n = 20), or both volatile and succinylcholine (n = 51). Eight (6.2%) cases occurred in the postanesthetic care unit. There were no reactions after discharge from the postanesthetic care unit. The most frequent clinical signs were hyperthermia (66.7%), sinus tachycardia (62.0%), and hypercarbia (51.9%). Complications occurred in 20.1% of patients, the most common complication being renal dysfunction. When 20 or more minutes between the first adverse sign and dantrolene treatment elapsed, complication rates increased to ≥30%. CONCLUSIONS: This is the first Canadian study in 3 decades to report nationwide data on MH epidemiology. Features that differ from earlier reports include a 15.5% incidence of reactions triggered by succinylcholine alone and lower complication rates. In agreement with previously published studies, we confirmed in this independent dataset that increased complication rates were associated with an increased time interval between the first adverse clinical sign and dantrolene treatment. This underscores the need for early diagnosis and rapid dantrolene access and administration in anesthetizing locations using either succinylcholine or volatile anesthetic drugs.