Gene x Environment interactions in speech sound disorder predict language and preliteracy outcomes

Few studies have investigated the role of gene x environment interactions (G x E) in speech, language, and literacy disorders. Currently, there are two theoretical models, the diathesis-stress model and the bioecological model, that make opposite predictions about the expected direction of G x E, because environmental risk factors may either strengthen or weaken the effect of genes on phenotypes. The purpose of the current study was to test for G x E at two speech sound disorder and reading disability linkage peaks using a sib-pair linkage design and continuous measures of socioeconomic status, home language/literacy environment, and number of ear infections. The interactions were tested using composite speech, language, and preliteracy phenotypes and previously identified linkage peaks on 6p22 and 15q21. Results showed five G x E at both the 6p22 and 15q21 locations across several phenotypes and environmental measures. Four of the five interactions were consistent with the bioecological model of G x E. Each of these four interactions involved environmental measures of the home language/literacy environment. The only interaction that was consistent with the diathesis-stress model was one involving the number of ear infections as the environmental risk variable. The direction of these interactions and possible interpretations are explored in the discussion.     

The standard gamble showed better construct validity than the time trade-off

BACKGROUND AND OBJECTIVE: There is little evidence for the relative cross-sectional validity of the standard gamble (SG) and time trade-off (TTO). We compared these preference-based instruments in patients with Irritable Bowel Syndrome (IBS). METHODS: Patients rated their own health on the SG and TTO and completed the disease-specific IBS questionnaire, the Brief Pain Inventory, the SF-36, the Sickness Impact Profile, and a global rating of disease severity. RESULTS: Mean scores of the 96 enrolled patients (mean age 39.5 years, 84.4% women) were 0.84 (standard deviation 0.16) for the SG and 0.76 (0.22) for the TTO. The correlation of the SG with the TTO was 0.36. For the SG, correlation coefficients with the IBS questionnaire domain scores ranged from 0.36 to 0.47, whereas those of the TTO were substantially lower (0.15-0.42). The SG also had higher correlations than the TTO with generic questionnaires (0.18-0.34 versus 0.13-0.26), Brief Pain Inventory (0.27 versus 0.11), global rating of disease severity (0.22 versus 0.10) as well as with SF-36-derived patient preferences (0.31-0.43 versus 0.27-0.31). CONCLUSIONS: The higher correlations of the SG with validation measures indicate that the SG better reflects health-related quality of life and patient preferences compared to the TTO.     

Rapid rise in the cost of targeted cancer therapies for Medicare patients with solid tumors from 2006 to 2015

BackgroundInflation-adjusted cancer costs in the United States have increased 40% in the last decade, leading to increasing financial burden on both payers and patients. Patients under 65 show substantial increases in utilization of expensive targeted therapy anticancer agents; however, patients aged 65+ account for the majority of new malignancies. Utilization and cost trends for these emerging agents have not been examined in detail in the Medicare population.Patients and methodsRetrospective prevalent cohort analysis of patients 65+ with any stage of invasive lung, breast, colorectal, or prostate cancer, receiving systemic therapy drawn from the United States Medicare 5% fee-for-service sample claims (2005–2015). Yearly trends in utilization and associated costs were modeled with adjustment for inflation, demographics, and comorbidities.ResultsAmong Medicare beneficiaries with fee-for-service and Part D enrollment who were receiving some type of systemic anticancer therapy, there were 9230 patients with colorectal, 32,738 patients with breast, and 16,278 patients with lung cancers identified from 2006 to 2015, and 19,295 patients with prostate cancer from 2009 to 2015. The share of cancer costs to Medicare attributable to targeted therapies, increased dramatically for prostate cancer (1.7% to 19.4%), lung cancer (6.7% to 19.4%), colorectal cancer (11.7% to 22.2%), and breast cancer (15.8% to 25.5%). Although the proportion of patients receiving targeted therapies remained stable, mean per-patient cancer costs increased dramatically from 2006 to 2015 for patients with lung or prostate cancer receiving targeted therapy and for patients with breast cancer receiving non-hormonal targeted therapies. Targeted agents for these cancers showed substantial inflation-adjusted price growth over this time period.     

Treatment of Metastatic Urothelial Carcinoma After Previous Cisplatin-based Chemotherapy for Localized Disease: A Retrospective Comparison of Different Chemotherapy Regimens

BackgroundOptimal chemotherapy for patients who received cisplatin for localized urothelial carcinoma (UC) and develop metastatic disease is unclear. We compared the efficacy of platinum-based (PBC) versus non–platinum-based (NPBC) first-line chemotherapy for metastasis.Patients and MethodsData were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3024 patients from 28 international academic centers from 2005 to 2012. Patient inclusion criteria included: (1) predominant UC; (2) any primary tumor site; (3) cT2-4, cN0-N2, cM0; (4) prior receipt of perioperative/radiation cisplatin-containing chemotherapy; and (5) receipt of cytotoxic chemotherapy in the first-line metastatic setting. Multivariate Cox proportional hazards models were used to show progression-free survival (PFS) and overall survival (OS) from the first day of chemotherapy for metastatic disease to date of censor.ResultsEligibility criteria was met by 132 patients (n = 74 PBC; n = 58 NPBC). The median OS was 8.13 months (interquartile range, 4.87-16.64 months) and 8.77 months (interquartile range, 4.01-13.49 months) for PBC and NPBC, respectively. Neither OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.64-1.69; P = .87) nor PFS (HR, 0.86; 95% CI, 0.56-1.31; P = .48) differed for PBC versus NPBC. However, for patients who received chemotherapy more than a year after perioperative/radiation chemotherapy, OS was superior for PBC over NPBC (HR, 0.31; 95% CI, 0.10-0.92; P = .03).ConclusionsThere is no significant outcome difference between PBC and NPBC in patients with metastatic UC who previously received cisplatin-based chemotherapy for localized disease. However, if over a year has elapsed, return to PBC is associated with superior OS.     

HER2 testing in breast cancers: comparison of assays and interpretation using ASCO/CAP 2013 and 2018 guidelines

Breast Cancer Research and Treatment - HER2 overexpression and gene amplification are routinely tested by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. In...     

Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil

5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous and can be treated with reduced 5-FU dosing. We describe a patient with a genotype associated with near complete absence of DPD function, and severe and likely fatal toxicity with 5-FU treatment. The patient was treated effectively with alternative systemic therapy. Routine pretreatment DPYD genotyping is recommended by the European Medicines Agency, and guidelines for use of 5-FU in DPD deficient patients are available. However, outside the province of Quebec, routine pretreatment screening for DPD deficiency remains unavailable in Canada. It is likely our patient would have died from 5-FU toxicity under the current standard of care, but instead provides an example of the potential benefit of DPYD screening on patient outcomes.