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Despite the efficacy of tyrosine kinase inhibitors (TKIs) across multiple cancers, side effects including treatment-related diarrhea can impede a patient's ability to reach therapeutic doses or stay on therapy. Below, we present the case of a 72-year-old patient with metastatic papillary renal cell carcinoma recurrent despite nephrectomy. Over the course of treatment, the patient received multiple different tyrosine kinase inhibitors with varying efficacy. Treatment with the TKI cabozantinib after failure of two prior TKIs resulted in a clinical response with shrinkage of his nodal metastatic disease. However, the severe treatment-related diarrhea refractory to conventional management required both dose holds and dose reductions of cabozantinib. Off-label administration of crofelemer, a novel FDA-approved antidiarrheal agent, successfully controlled the treatment-related diarrhea and allowed resumption and partial dose increase of cabozantinib. This case suggests that crofelemer could be a viable therapeutic strategy to address TKI-induced diarrhea.

ImportanceCombining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown.ObjectiveTo determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer.Design, setting, and participantsPatients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015.InterventionsCetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient.Main outcomes and measuresThe primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response.ResultsAmong 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13).Conclusions and relevanceAmong patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.Trial registrationclinicaltrials.gov identifier: NCT00265850.

As US consumers increasingly turn to multiple financial institutions, multiple FinTech providers and multiple payment apps, getting a full picture of the consumer's wallet is rare. Drawing on data collected through the Survey and Diary of Consumer Payment Choice — a representative survey of US consumers conducted since 2008 — this paper provides insights into US consumers' adoption of bank accounts and payment instruments, their recent use of payment instruments, their payment choices for purchases and bills, and the evolution in their practices over the last decade of innovation in payments. [ABSTRACT FROM AUTHOR]

BackgroundBRAF-mutant metastatic colorectal cancers (mCRCs) share many clinicopathologic features with right-sided colon tumors, including frequent peritoneal involvement. Because of the poorer outcomes associated with BRAF mutations, early enrollment in clinical trials has been encouraged. However, the use of standard eligibility and assessment criteria, such as measurable disease, has anecdotally impeded patient accrual and restricted appraisal of treatment response. We investigated whether the presence of a BRAF V600E mutation is differentially associated with sites and appearance of metastatic disease in patients matched by primary tumor location.MethodsA total of 40 patients with BRAF-mutant mCRC were matched to 80 patients with BRAF wild-type mCRC by location of primary tumor (right or left colon; rectum), sex, and age. Associations between BRAF mutation status and clinicopathologic characteristics and metastatic sites were analyzed using proportion tests. Survival was summarized with Kaplan-Meier and Cox regression methods.ResultsThe distribution of primary tumor locations was: 60% right colon, 30% left colon, and 10% rectum. Compared with BRAF wild-type tumors, BRAF-mutant tumors more commonly associated with peritoneal metastases (50% vs 31%; P=.045) and ascites (50% vs 24%; P=.0038). In patients with left colon primaries, BRAF mutations were associated with more frequent ascites (58% vs 12%; P=.0038) and less frequent liver metastases (42% vs 79%; P=.024). Among patients with right colon primaries, no significant difference in sites of disease by BRAF mutation status was observed. Disease was not measurable by RECIST 1.1 in 24% of patients with right-sided primary tumors, irrespective of BRAF mutation status. In the BRAF-mutated cohort, ascites correlated unfavorably with survival (hazard ratio, 2.35; 95% CI, 1.14, 4.83; P=.02).ConclusionsGreater frequency of ascites and peritoneal metastases, which pose challenges for RECIST 1.1 interpretation of therapeutic outcomes, are seen with BRAF-mutant mCRC, even when patients are matched for primary tumor location.

UnlabelledPatients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in 9 patients (35%). In the remaining 17, 90.3% (95% confidence interval, 73.1%-97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r = 0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful.SignificancePrecision medicine efforts in biliary and pancreatic cancers have been frustrated by difficulties in obtaining adequate tumor tissue for next-generation sequencing. cfDNA sequencing reliably and accurately detects tumor-derived mutations, paving the way for precision oncology approaches in these deadly diseases.

Using transaction data from a US consumer payments diary, we revisit the credit card debt puzzle--a scenario in which consumers revolve credit card debt while also keeping liquid assets as bank account deposits. This scenario is very common: 42 percent of consumers in our sample were borrower-savers in 2019 (those who carry $100 or more in credit card debt and $100 or more in liquid assets). We explain the puzzle by showing that consumers need their liquid assets to pay monthly bills and other necessary expenses, including mortgage or rent. More than 80 percent of bills by value were paid out of bank accounts and could not be charged to credit cards, so bank account balances were needed to cover those basic expenses. On average, borrower-savers' credit card debt exceeded their liquid assets. The average borrower-saver carried almost $6,400 in unpaid credit card debt and had $5,400 in liquid assets, including checking and savings accounts, cash, and general-purpose prepaid cards. Only 40 percent of borrower-savers had liquid assets greater than their unpaid credit card balance. In addition, borrower-savers' monthly expenses (bills and purchases) averaged 77 percent of their liquid assets, not leaving enough to repay their credit card debt. On average, the value of their liquid assets could cover only about 60 percent of their unpaid debt plus monthly bills. In almost every category of assets or debts, both housing- and nonhousing-related, borrower-savers were significantly worse off financially than savers. Thus, the differences between borrower-savers and savers are much broader than just their credit card debt and bank account balances; the differences extend to mortgage debt and home equity. Even when we control for income and demographics in a regression, we find that carrying a mortgage or other debt (such as auto or educational loans) is associated with a higher probability of revolving on a credit card, suggesting that various types of household debt are complements rather than substitutes. During the COVID-19 pandemic in 2020, consumers' unpaid credit card debt decreased, and their liquid assets increased, so the fraction of borrower-savers dropped to 35 percent of the sample. JEL classification: D12, D14, E42 Key words: credit card debt, liquid assets, consumer payments, Working Paper 2022-9 August 2022 I. Introduction The credit card debt puzzle refers to a scenario in which consumers carry--or, 'revolve'--unpaid credit card debt while maintaining some liquid assets, typically [...]

Using a representative sample of the U.S. adult population, we analyze which payment methods consumers use to pay other consumers (p2p) and how these choices depend on transaction and demographic characteristics. We additionally construct a random matching model of consumers with diverse preferences over the use of different payment methods for p2p payments. The random matching model is calibrated to the share of p2p payments made with cash, paper check, and electronic technologies observed from 2015 to 2019. We find about two thirds of consumers have a first p2p payment preference of cash. The remaining one third rank checks first. Approximately 93 percent of consumers rank electronic technologies second. Our empirical analysis finds that the most significant factors in determining the payment method used are the transaction value and the age and education of the payer. JEL classification: D9, E42 Key words: consumer payment choice, person-to-person payments, electronic payments, mixed logit, machine learning, random matching, Working Paper 2021-11 February 2021 1. Introduction Consider the following scenarios: A friend purchased something for you and now she must be repaid. Or maybe you want to give her [...]

The COVID-19 pandemic caused large changes in consumer spending, including how people make their payments. For employed consumers, the pandemic also changed workplace behaviour, with about one-third of workers continuing to work from home every day as of September 2020. Using data from a nationally representative survey of US consumers collected before and during the pandemic, this paper analyses changes in workplace and payment behaviour during the pandemic. The study finds that, compared with their payment behaviour in 2019, consumers had shifted some of their purchases from in person to online by the autumn of 2020, significantly reduced their use of cash for purchases, and shifted their person-toperson (P2P) payments away from paper-based instruments (ie cash and cheques). These changes are consistent with what we might expect, as many people were less able or willing to shop in person. The adoption of electronic P2P payments increased, especially the use of payment apps such as PayPal, Venmo and Zelle. In comparison with consumers who worked at least partly in person, consumers who worked exclusively from home during the pandemic made a significantly higher proportion of their payments online or through mobile devices, and were less likely to use cash at all, even after controlling for income and education levels. In contrast, payment behaviour changes that took place from 2018 to 2019 were smaller in magnitude and largely insignificant, suggesting that COVID-19 likely accelerated any longerterm trends. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinical records of all guinea pigs diagnosed with a lower urinary tract disease in a single veterinary hospital, over a period of 14 years (2004–2018), were searched in order to characterize this population and investigate the potential association between the different features relating to the animal and the clinical approach toward them. A total of 117 clinical cases were identified, corresponding to 57 animals. The formation of stones in the urinary tract (urolithiasis) was the most common diagnosis (n = 52; 44.4%), followed by bladder inflammation (cystitis) and/or a urinary tract infection (UTI). Several associations were identified, showing that female guinea pigs were more likely than the male ones to have a previous family history of urinary disease, to present abnormal micturition signs at admission, and to have recurrence. Moreover, males were more prone to urolithiasis and females to cystitis/UTI, and animals diagnosed with cystitis/UTI frequently had more clinical urinary signs and abdominal pain on palpation compared to those diagnosed with urolithiasis. Finally, the use of potassium citrate and the urethrotomy approach were associated with a better therapeutic response. Further studies are needed in larger populations of guinea pigs to confirm the present findings, especially as some of them were described for the first time. The clinical records of all guinea pigs diagnosed with a lower urinary tract disease in a single veterinary hospital, over a period of 14 years (2004–2018), were retrospectively searched in order to characterize this population and investigate the potential association between the epidemiological and clinical variables. A total of 117 clinical cases were identified, corresponding to 57 animals. Urolithiasis was the most common diagnosis (n = 52; 44.4%), followed by cystitis and/or a urinary tract infection (UTI). Several statistically significant associations (p < 0.05) were found between different variables, showing that female guinea pigs were more likely than the male ones to have a previous family history of urinary disease, to present dysuria and stranguria at admission, and to suffer recurrence. Moreover, males were more prone to urolithiasis and females to cystitis/UTI, and animals diagnosed with cystitis/UTI frequently had more clinical urinary signs and abdominal pain on palpation compared to those diagnosed with urolithiasis. Finally, the use of potassium citrate and the urethrotomy approach were associated with a better therapeutic response. Further studies are needed in larger populations of guinea pigs to confirm the present findings, especially as some of them were described for the first time. [ABSTRACT FROM AUTHOR]