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PurposeDiarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea.MethodsThis paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management.ResultsIn the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed-and continue to be refined-to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea.ConclusionsContinued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity.

A random sample of primary grade teachers from across the United States was surveyed about their instructional practices in handwriting. Nine out of every ten teachers indicated that they taught handwriting, averaging 70 minutes of instruction per week. Only 12% of teachers, however, indicated that the education courses taken in college adequately prepared them to teach handwriting. Despite this lack of formal preparation, the majority of teachers used a variety of recommended instructional practices for teaching handwriting. The application of such practices, though, was applied unevenly, raising concerns about the quality of handwriting instruction for all children.

In this study, we examined whether early, supplemental strategy instruction in planning helped ameliorate writing difficulties. Second-grade students experiencing difficulty learning to write were taught a strategy for planning and writing stories. Learning to use the strategy had a positive effect on writing, as students' stories became more complete and, with the exception of 1 student, qualitatively better. Collateral improvements in an uninstructed genre, personal narratives, also occurred for all but 1 student. These positive effects were generally maintained over time and in some instances exceeded posttreatment effects.

Objectives. We assessed young adults' exposure to the tobacco industry marketing strategy of sponsoring social events at bars, nightclubs, and college campuses. Methods. We analyzed data from the 2001 Harvard College Alcohol Study, a random sample of 10904 students enrolled in 119 nationally representative 4-year colleges and universities. Results. During the 2000-2001 school year, 8.5% of respondents attended a bar, nightclub, or campus social event where free cigarettes were distributed. Events were reported by students attending 118 of the 119 schools (99.2%). Attendance was associated with a higher student smoking prevalence after we adjusted for demographic factors, alcohol use, and recent bar/nightclub attendance. This association remained for students who did not smoke regularly before 19 years of age but not for students who smoked regularly by 19 years of age. Conclusions. Attendance at a tobacco industry-sponsored event at a bar, nightclub, or campus party was associated with a higher smoking prevalence among college students. Promotional events may encourage the initiation or the progression of tobacco use among college students who are not smoking regularly when they enter college. (Am J Public Health. 2005;95:138-144. doi: 10.2105/ AJPH.2003.026054)

Objective. Young smokers commonly identify themselves as "social smokers," a pattern of smoking behavior that is poorly understood. We assessed the prevalence and correlates of social smoking among US college students. Methods. Cross-sectional survey of a random sample of 10 904 students enrolled at 119 nationally representative US colleges in 2001. Results. A total of 51% of 2401 current (past 30-day) smokers were social smokers. (To assess social smoking, students were asked, "In the past 30 days, do you smoke mainly when you are with people, mainly when you are alone, or do you smoke as often by yourself as with others?" Students who stated that they smoked mainly with others rather than alone or equally by themselves and others were defined as social smokers for this analysis.) Social smoking was independently associated with a lower frequency and intensity of tobacco use, less nicotine dependence, less intention to quit, and fewer recent quit attempts. Conclusions. Social smoking is a distinct pattern of tobacco use that is common among college students and may represent a stage in the uptake of smoking. Pediatrics 2004;114:1028-1034; tobacco, smoking, young adults, patterns of use., ABBREVIATION. CAS, College Alcohol Study. Recent trends in tobacco use have focused public health attention on young adults (aged 18-24 years). From 1993 to 2000, the prevalence of smoking by [...]

The optimal sequencing of systemic treatments for metastatic urothelial cancer (mUC) is unknown. We assessed the efficacy of infigratinib, a fibroblast growth factor receptor (FGFR) 1 to 3 inhibitor, in 67 patients with FGFR3 -altered mUC by line of therapy. Objective response rates were 31% (early-line setting) and 24% (≥2nd-line setting). Infigratinib has notable activity in mUC regardless of line of therapy. Introduction: To describe the efficacy of infigratinib, a potent, selective fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor, across lines of therapy (LOT) in patients with metastatic urothelial cancer (mUC). Patients and Methods: Eligible patients had mUC and prior platinum-based chemotherapy, unless contraindicated, and activating FGFR3 mutation/fusion. Patients received infigratinib 125 mg orally daily (3 weeks on/1 week off) in a single-arm, openlabel study. Primary endpoint: investigator-assessed confirmed objective response rate (ORR). Disease control rate (DCR), progression-free survival (PFS), best overall response (BOR) that included unconfirmed responses, and overall survival (OS) were also assessed. Subgroup analysis of efficacy and safety outcomes by LOT was performed. Results: Sixty-seven patients were enrolled; 13 (19.4%) received infigratinib as early-line therapy for mUC due to ineligibility to receive platinum-based chemotherapy. Overall, ORR was 25.4% (95% CI 15.5-37.5) and DCR was 64.2% (95% CI 51.5-75.5). ORR was 30.8% (95% CI 9.1-61.4) with early-line infigratinib and 24.1% (95% CI 13.5-37.6) for =2 LOT. DCR was 46.2% (95% CI 19.2-74.9) for early-line and 68.5% (95% CI 54.4-80.5) for =2 LOT. PFS and OS appeared similar in both groups. Thirteen of 59 patients with a bladder primary tumor received early-line treatment with an ORR of 30.5% (95% CI 9.1-61.4), and 46 received =2 LOT with an ORR of 20.3% (95% CI 9.4-33.9); BOR was 38.5% (95% CI: 13.9-68.4%) and 42.6% (95% CI: 29.2-56.8%) in the early-line and salvage settings, respectively. Eight patients with upper tract urothelial carcinoma received salvage therapy (ORR, 50.0%; DCR, 100.0%). No significant differences in toxicities between LOT were observed. Conclusion: Infigratinib has notable activity in patients with mUC regardless of LOT. The findings support the evaluation of infigratinib across different settings in mUC. [ABSTRACT FROM AUTHOR]