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OBJECTIVE: The objective of the study was to evaluate the impact of rosacea on self-perception, emotional, social, and overall well-being and quality of life in individuals with erythematotelangiectatic rosacea (ETR) and papulopustular rosacea (PPR). DESIGN: We distributed a cross-sectional email invitation for participants in the United States to fill out a web-based survey. PARTICIPANTS: We included adults who reported having previously received a diagnosis of erythematotelangiectatic rosacea or papulopustular rosacea. MEASUREMENTS: Questionnaires measured the psychosocial aspects of rosacea, including the Satisfaction With Appearance Scale and modified Satisfaction With Appearance Scale questionnaires, Impact Assessment for Rosacea Facial Redness, Rosacea-Specific Quality-of-Life questionnaire, and RAND 36-Item Short Form Health Survey. The Impact Assessment for Rosacea Facial Bumps or Pimples was administered to the papulopustular rosacea cohort. RESULTS: Six hundred participants enrolled and completed the survey, with most rating their rosacea as mild or moderate (ETR: 95.6%; PPR: 93.7%). In the erythematotelangiectatic rosacea and papulopustular rosacea cohorts, respectively, 45 and 53 percent disagreed/strongly disagreed that they were satisfied with their appearance due to rosacea; 42 and 27 percent agreed/strongly agreed that they "worry how people will react when they see my rosacea"; and 43 and 59 percent agreed/strongly agreed that they feel their rosacea is unattractive to others. Rosacea-Specific Quality-of-Life total and domain scores indicated negative impact of rosacea for both cohorts. Both cohorts reported worse 36-item Short Form Health Survey overall and domain scores than population norms in the United States. CONCLUSION: Rosacea had wide-ranging, negative effects on self-perceptions and emotional, social, and overall well-being as well as rosacea-specific quality of life. Overall, both erythematotelangiectatic rosacea and papulopustular rosacea cohorts reported a substantial negative impact of rosacea on quality of life on a range of instruments.

Cyclopiazonic acid decreases spontaneous transient depolarizations in guinea pig mesenteric lymphatic vessels in endotheliumdependent and -independent manners. Am J Physiol Heart Circ Physiol 286: H2287-H2295, 2004. First published February 19, 2004; 10.1152/ajpheart.00739.2003.--Guinea pig mesenteric lymphatic vessels exhibit vasomotion through a pacemaker mechanism that involves intracellular [Ca.sub.2+] release and resultant spontaneous transient depolarizations (STDs) of the smooth muscle membrane potential. This study presents a detailed characterization of the effects of cyclopiazonic acid (CPA) on this pacemaker activity. Microelectrode recordings from smooth muscle in vessel segments revealed that application of CPA (1-10 [micro]M) caused a hyperpolarization accompanied by a decrease in the frequency and amplitude of STDs. The CPA-induced hyperpolarization was abolished after destruction of the endothelium and in the presence of [N.sup.G]-nitro-L-arginine (100 [micro]M) or 1H-[1,2,4]oxadiazolol-[4,3-a]quinoxaline- 1-one (10 [micro]M), which suggests a contribution of endothelium-derived nitric oxide (EDNO) in this response. In the absence of EDNO-induced effects, CPA decreased the frequency and amplitude of STDs recorded before and in the presence of the thromboxane [A.sub.2] mimetic U-46619, norepinephrine, or thimerosal. CPA abolished U-46619-induced vasomotion as determined by measurement of constriction-associated intracellular [Ca.sup.2+] concentration using the ratiometric [Ca.sup.2+] indicator fura-2. The endothelial actions of CPA were compared with those of ACh, which is known to cause EDNO release in this preparation. Although CPA and ACh both increased endothelial intracellular [Ca.sup.2+] concentration and depolarized the membrane potential, the kinetics of action for both parameters were markedly slower for CPA than ACh. These results suggest that CPA first hyperpolarizes the lymphatic smooth muscle and decreases STD frequency and amplitude through endothelial release of EDNO, and second, consistent with the action of CPA to inhibit sarcoplasmic reticulum [Ca.sup.2+]-ATPase and deplete [Ca.sup.2+] stores, it further reduces STD activity. Inhibition of the lymphatic smooth muscle pacemaker mechanism is thought to abolish agonist-induced vasomotion. pumping; nitric oxide; smooth muscle; lymphatic vasomotion

Objectives: We evaluated adherence of human epidermal growth factor receptor-2 testing using immunohistochemistry and fluorescence in situ hybridization, as well as adjuvant trastuzumab treatment according to Canadian guidelines, and predictors of trastuzumab use in early-stage breast cancer in Ontario. Methods: Retrospective cohort of early-stage breast cancer patients identified in the Ontario Cancer Registry. Human epidermal growth factor receptor-2 test type, sequence, result(s), tumor grade, and hormone receptor status were abstracted from Ontario Cancer Registry pathology reports. Trastuzumab treatment was determined from provincial cancer agency records. Other variables were determined from administrative data sources. Logistic regression models were used to estimate adjusted odds ratios for factors associated with guideline adherence. Results: The first human epidermal growth factor receptor-2 test result was the strongest predictor of confirmatory testing (p < 0.05). Human epidermal growth factor receptor-2 testing by immunohistochemistry accounted for the majority of documented first tests (94%; n = 8249). Overall, 27% (n = 2360) of tested patients received a second test by fluorescence in situ hybridization (46%) or immunohistochemistry (49%) assay. Most human epidermal growth factor receptor-2 equivocal patients (89%; n = 784) received a confirmatory test. Among human epidermal growth factor receptor-2-positive patients, only 57% (n = 385) received trastuzumab treatment within the study period. Human epidermal growth factor receptor-2 status was the strongest predictor of trastuzumab use. Younger patients (<70 years at diagnosis) and negative hormone receptor status had higher odds of trastuzumab treatment (p < 0.05) compared to older and positive hormone receptor status patients. Conclusions: Immunohistochemistry use as a first test was largely consistent with Canadian guidelines; however, immunohistochemistry was frequently used as a confirmatory test, which is not guideline-concordant. Monitoring these testing and treating patterns is necessary to optimize health outcomes associated with trastuzumab. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic skin condition characterized by persistent central facial erythema. To explore the burden of illness of rosacea in US adults, a cross-sectional web-based survey was conducted. Participants answered questions on sociodemographics, clinical characteristics, bothersome symptoms, coping and avoidance behaviors, self-perceptions, and health care resource utilization, and completed 2 quality of life instruments, the 21-item rosacea-specific quality of life questionnaire (RosaQoL) and the 36-item Short Form Health Survey (SF-36). This paper reports the data from the 409 respondents with erythematotelangiectatic rosacea (ETR), analyzed by erythema severity. Mean age was 53.1 years; mild, moderate, or severe erythema was reported by 63.6%, 32.0%, and 4.4% of participants, respectively. Blushing/flushing and bumps/pustules were the most bothersome symptoms across severity subgroups. Participants in all subgroups coped with rosacea by applying make-up and managing their stress and anxiety, and tried to prevent rosacea flares by avoiding sun exposure, specific skin care products, and other triggers. Self-perceptions differed by severity subgroup: satisfaction with facial appearance significantly decreased, and worrying about how people will react and feelings of unattractiveness to others significantly increased, with greater erythema severity (all P less than 0.01). Treatment or assessment of rosacea was sought by 20% of participants in the past 3 months, most commonly from a dermatologist. Metronidazole was the most frequently prescribed topical product across severity subgroups, whereas doxycycline and other oral antibiotics were prescribed most frequently in the severe erythema subgroup. RosaQoL emotional domain scores increased with erythema severity (P equals 0.0035), but none of the SF-36 domain scores differed significantly by erythema severity. These results demonstrate that rosacea is associated with a substantial burden of illness that spans all levels of erythema severity in patients with ETR. Feelings of unattractiveness and the adverse impact of rosacea on emotional quality of life increased with erythema severity. J Drugs Dermatol. 2018;17(2):150-158.

Objective: Evaluate patients' perceptions of rosacea symptoms and treatments. Design: Cross-sectional, web-based survey conducted from May 8 to July 1,2015. Setting: E-mail invitation. Participants: Male and female adults in the United States who self-reported having a physician's diagnosis of rosacea. Measurements: Sociodemographic and clinical characteristics were collected for eligible respondents using the Self-Assessment of Rosacea Facial Redness scale and the Symptom Assessment for Rosacea Facial Bumps and Pimples questionnaire. Respondents were instructed how to differentiate erythematotelangiectatic rosacea and papulopustular rosacea. Use of different treatments and satisfaction with treatment were assessed, as were coping mechanisms. Results: More than 4,000 individuals responded and 600 completed the survey. The participants' mean age was 51.7 years and more than 90 percent rated their rosacea severity as mild or moderate. Most practiced stress and/or anxiety management, used makeup to cover rosacea, used sun protection, and changed their exercise regimens to cope with rosacea flare-ups. Participants reported avoiding sun exposure, hot baths and saunas, and specific skin care products to circumvent potential rosacea flare-ups. More than half (55.7%) had used a prescribed topical agent for rosacea in the preceding month, and 26.3 percent had used a prescribed oral antibiotic. Fewer than half were satisfied with treatment outcomes. Conclusion: Despite the chronic nature of rosacea, participants commonly used prescription agents only to treat flare-ups and relied on sun protection and other avoidance mechanisms to reduce their frequency. Education is needed to communicate the long-term nature of rosacea and the need for continued treatment to maintain long-term control., Competing Interests: Disclosure:This study was sponsored by Allergan plc, Dublin, Ireland. Manuscript preparation and editorial assistance was provided to the authors by Michael L. Pucci, PhD, of Peloton Advantage, Parsippany, New Jersey, and was funded by Allergan plc. Neither honoraria nor other form of compensation were made to the authors for authorship or any other activities related to preparation or submission of this manuscript. Related to the subject area of rosacea, Dr. Del Rosso serves as a consultant, speaker, and researcher for Allergan, Bayer Dermatology, and Galderma.

Background: Uncertainty about human epidermal growth factor receptor-2 (HER2) testing practice in Canada continues to hinder efforts to improve personalized medicine. Pathologists routinely perform HER2 assessment for all tumors > 1 cm, and pathology is reported centrally to the provincial cancer registry., Objectives: To understand patterns of HER2 test documentation for early-stage breast cancer (BC) patients in Ontario's centralized pathology reporting system., Study Design: Retrospective cohort study of central HER2 test documentation in early-stage BC patients diagnosed in 2006-2007., Methods: Cohort and staging information was derived from cancer registry and admissions data. Linkage across administrative databases provided data on surgical and radiologic treatment, sociodemographic factors, diagnosis setting, and comorbidities. Pathology reports from the provincial cancer registry were reviewed for HER2 testing, hormone receptor, and grade. Unadjusted and adjusted odds ratios were calculated to determine factors related to HER2 documentation., Results: A HER2 test was documented for 66% of 13,396 patients. HER2 documentation was associated with stage, hormone receptor, and tumor grade documentation. Higher stage and grade at diagnosis were also associated with HER2 documentation. All models suggested variable regional documentation patterns. Documentation did not differ by sociodemographic factors, presence of comorbidities, or surgical procedure., Conclusions: Despite a universal testing policy, the rate of centralized HER2 test documentation was lower than expected and related to disease severity. Differences in regional reporting likely reflect ascertainment bias inherent to centralized pathology reporting rather than testing access. Improved HER2 reporting is encouraged for cancer registration, quality-of-care measurement, and program evaluation.

Objective: Decision makers must make decisions without complete information. That uncertainty can be decreased when economic evaluations use local data and can be quantified by considering the variability of all model inputs concurrently per international evaluation guidelines. It is unclear how these recommendations have been implemented in evaluations of targeted cancer therapy. By using economic evaluations of adjuvant trastuzumab, we have assessed the extent to which decision support recommendations were adopted., Study Design: Systematic review., Methods: Published economic evaluations of adjuvant trastuzumab treatment in early-stage breast cancer were examined as an established example of targeted therapy. Canadian, United Kingdom, and US economic evaluation guidelines were reviewed to establish extraction criteria. Extraction characterized the use of effectiveness evidence and local data sources for model parameters, sensitivity analysis methods (scenario, univariate, multivariate, and probabilistic), and uncertainty representation (ie, cost-effectiveness plane, scatterplot, confidence ellipses, tornado diagrams, cost-effectiveness acceptability curve)., Results: Fifteen economic evaluations of adjuvant trastuzumab were identified in the literature. Local data were used to estimate costs (15 of 15) and utilities rarely (2 of 15) but not trastuzumab efficacy. Univariate sensitivity analysis was most common (12 of 15), whereas probabilistic analysis was less frequent (10 of 15). Two-thirds of all studies provided visual representation of results and decision uncertainty., Conclusion: Authors of adjuvant trastuzumab economic evaluations rarely use local data beyond costs. Quantification of uncertainty and its representation also fell short of guideline recommendations. This review demonstrates that economic evaluations of adjuvant trastuzumab, as an example of targeted cancer therapy, can be improved for decision-making support.