PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

More than a message: framing public health advocacy to change corporate practices.

Framing battles in public health illustrate the tension in our society between individual freedom and collective responsibility. This article describes how two frames, market justice and social justice, first articulated in a public health context by Dan Beauchamp, influence public dialogue on the health consequences of corporate practices. The authors argue that public health advocates must articulate the social justice values motivating the changes they seek in specific policy battles that will be debated in the context of news coverage. The authors conclude with lessons for health education practitioners who need to frame public health issues in contentious and controversial policy contexts. Specific lessons include the importance of understanding the existing values and beliefs motivating the public health change being sought, the benefits of articulating core messages that correspond to shared values, and the necessity of developing media skills to compete effectively with adversaries in public debate.     

Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease

Recent work has suggested that patients with damage to temporal lobe structures, such as patients with Alzheimer's Disease (AD), lose information from memory at an abnormally rapid rate. In contrast, data from other studies suggest that the rate of forgetting in AD is normal. In the present study, 62 patients with mild to moderate AD and 64 elderly controls were tested for their immediate and delayed recall of a short verbal passage and a modified Rey complex figure. The results suggest that although AD patients recalled less than controls, they did not forget at a faster rate during the 30 minute retention interval, supporting the finding that these memory impaired patients do not have an abnormal rate of forgetting. The data also suggest that poor initial encoding of the stimuli may be the cause of the AD patients' impaired recall.     

Gangliosides of human melanoma: altered expression in vivo and in vitro

The ganglioside composition of human melanoma was analyzed in five sets of tumor specimens obtained directly from surgery, from the autologous tissue culture cell lines, and from the autologous cell lines grown in athymic nude mice. Total gangliosides of these 15 melanoma specimens were isolated and purified, and the amount of each component ganglioside was analyzed by thin-layer chromatography and a thin-layer chromatography scanner. The ganglioside composition of the five surgical melanoma specimens clearly exhibited different patterns from each other. Moreover, none of the autologous cultured melanomas possessed the same ganglioside composition as their original biopsied tumors. However, when these melanoma cell lines were transplanted into nude mice, the ganglioside composition was converted back to the same ganglioside pattern as in the original surgical specimens. The results support the view that changes in the ganglioside composition of melanoma during in vitro growth are caused by the culture environment rather than by selection of melanoma cells with a particular genotype. Reestablishment of the original ganglioside patterns after passage in nude mice provides clear evidence that in vivo expression of gangliosides is a conserved and stable function specified by the human melanoma cells.     

Comparison of the detection of subtle changes in myocardial regional systolic function using qualitative and semi-quantitative techniques.

PURPOSE: To evaluate qualitative wall motion assessment vs. quantitative wall thickening for the assessment of subtle changes in myocardial systolic function using cine MRI. METHODS: Cine MR images were obtained in 5 canines with a significant coronary artery stenosis and in 2 controls on a 1.5T scanner. Qualitative results were obtained using a numerical scoring system; quantitative analysis was performed using a semi-automatic segmentation program. The techniques were matched and compared using Spearman correlations. RESULTS: All correlations in the experimental group revealed significant but weak to moderate relationships between the qualitative and quantitative results (e.g., at-risk tissue rho = 0.363, p < 0.0001; remote tissue rho = 0.275, p = 0.0002), with each identifying changes in regional function that ensued following creation of the stenosis. Intra-observer variability was reasonable in both methods when repeat analysis on a subset of the data was performed, with both techniques showing a significant correlation between the repeated measurements (quantitative - rho = 0.52, p < 0.0001; qualitative - rho = 0.54, p < 0.0001). CONCLUSION: Both methods were able to detect very limited wall motion abnormalities present in the canines with significant stenosis and either method gives comparable results.