[Measures to Ensure Ongoing Medical Laboratory Support of the Emergency Department].

Following the accreditation of this hospital as an Emergency and Critical Care Center and the subsequent establishment of an emergency intensive care unit in April 2013, walk-in patients of the Emergency Department now total over 60,000 annually, with 10,000 arriving by ambulance. Out-of-hours medical laboratory services in this hospital commenced in 1972, providing services including blood analysis and blood product provision. Since the establishment of the Emergency and Critical Care Center, an increase in the number of severe cases has also led to an increase in blood transfusions, requiring a specialized response from the Medical Laboratory. We describe measures taken by the Medical Laboratory to continue ongoing laboratory support of the Emergency Department. [Review].

Phase I and pharmacokinetic study of 3'-C-ethynylcytidine (TAS-106), an inhibitor of RNA polymerase I, II and III,in patients with advanced solid malignancies.

BACKGROUND: TAS-106 is a novel nucleoside analog that inhibits RNA polymerases I, II and II and has demonstrated robust antitumor activity in a wide range of models of human cancer in preclinical studies. This study was performed to principally evaluate the feasibility of administering TAS-106 as a bolus intravenous (IV) infusion every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of TAS-106 as a single bolus IV infusion every 3 weeks. Plasma and urine sampling were performed during the first course to characterize the pharmacokinetic profile of TAS-106 and assess pharmacodynamic relationships. RESULTS: Thirty patients were treated with 66 courses of TAS-106 at eight dose levels ranging from 0.67-9.46 mg/m(2). A cumulative sensory peripheral neuropathy was the principal dose-limiting toxicity (DLT) of TAS-106 at the 6.31 mg/m(2) dose level, which was determined to be the maximum tolerated dose (MTD). Other mild-moderate drug-related toxicities include asthenia, anorexia, nausea, vomiting, myelosuppression, and dermatologic effects. Major objective antitumor responses were not observed. The pharmacokinetics of TAS-106 were dose-proportional. The terminal elimination half-life (t(1/2)) averaged 11.3 ± 3.3 h. Approximately 71% of TAS-106 was excreted in the urine as unchanged drug. Pharmacodynamic relationships were observed between neuropathy and: C(5min;) AUC(0-inf;) and dermatologic toxicity. CONCLUSIONS: The recommended phase II dose of TAS-106 is 4.21 mg/m(2). However, due to a cumulative drug-related peripheral sensory neuropathy that proved to be dose-limiting, further evaluation of this bolus every 21 day infusion schedule will not be pursued and instead, an alternate dosing schedule of TAS-106 administered as a continuous 24-hour infusion will be explored to decrease C(max) in efforts to minimize peripheral neuropathy and maximize antitumor activity.

A new multidimensional model of successful aging: perceptions of Japanese American older adults.

This study examined the concept of successful aging using an ethnographic grounded-theory approach. Seventy-seven Japanese American older adults participated in focus groups. Participants perceived successful aging as optimal functioning in the following areas: Physical health, psychological health, cognitive functioning, socialization, spirituality, and financial security. The content of each dimension represents both culture-specific and culturally-universal elements. This new multidimensional model of successful aging was compared to Rowe and Kahn's (The Gerontologist 37:433-440, 1997) and Phelan et al.'s frameworks (Journal of the American Geriatric Society 52:211-216, 2004) of successful aging. The model of successful aging generated from this study appears to be more comprehensive than existing models and incorporates sociocultural experiences.

Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells.

Notch signaling has previously been implicated in the regulation of the cell fate of intestinal epithelial cells. However, the expression and function of Notch ligands in the human intestine remain largely unknown. In the present study, we showed that Notch ligands Delta-like 1 (Dll1) and Delta-like 4 (Dll4) are expressed in a goblet cell-specific manner in human colonic tissue. Additionally, we found that Dll1 and Dll4 expression was regulated in-parallel with Atoh1 and MUC2, which are both under the control of the Notch-Hes1 signaling pathway. Because knockdown of Dll1 expression completely abrogated the acquisition of the goblet cell phenotype in Notch-inactivated colonic epithelial cells, we postulate that Dll1 might function as a cis-acting regulatory element that induces undifferentiated cells to become goblet cells. Our results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand.

The future of financing for long-term care: the Own Your Future campaign.

The purpose of this study was to examine the outreach effort and impact of a joint federal-state campaign, Own Your Future, promoting awareness and planning for long-term care (LTC) in the state of Washington. The study applied survey methodology to evaluate the extent of campaign dissemination, evidence of its impact on LTC planning behaviors, and barriers to purchasing private LTC insurance. A total of 3,198 survey responses from a randomly selected community sample and a Washington State employee sample (ages 51 to 71) were analyzed. Results indicated that the impact of the campaign was limited, both with respect to awareness of the campaign itself and to initiation of LTC planning behaviors. Quantitative data revealed a high prevalence of health-related problems (e.g., obesity, diabetes), inadequate knowledge of basic LTC-related information (e.g., cost, payers), and negative attitudes toward purchasing LTC insurance among respondents. Qualitative analyses suggested that respondents perceived significant problems related to affordability and accountability within the current LTC insurance industry. These possible barriers to the purchase of LTC insurance suggest targets to be addressed by policy makers seeking to find ways to offset the public costs of LTC.

Reporting Sexual Assault: Survivors' Satisfaction With Sexual Assault Response Personnel.

Although jurisdictions have attempted to improve their response procedures, sexual assault cases are often insufficiently investigated. This study examines the survey responses of 460 female sexual assault survivors regarding their experiences with response personnel. Overall satisfaction with response services was 66.1%. Victim advocates and forensic nurses received higher satisfaction ratings than did patrol officers, detectives, and State's Attorney's Office staff. The present study also found that 65% of the variance in overall satisfaction was accounted for by four personnel behaviors: respectful treatment, clearly explained procedures, believed their stories, and demonstrated cultural sensitivity. Policy implications and suggestions for future research are discussed.

Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial.

IMPORTANCE: Administration of gemcitabine-cisplatin, the current standard therapy for advanced biliary tract cancers, results in median progression-free survival and overall survival of 8.0 and 11.7 months, respectively. New treatments offering improved survival outcomes are therefore needed. OBJECTIVE: To evaluate the association between progression-free survival and the addition of nanoparticle albumin-bound (nab)-paclitaxel to gemcitabine-cisplatin for the treatment of patients with advanced biliary tract cancer. DESIGN, SETTING, AND PARTICIPANTS: This open-label, single-arm, phase 2 clinical trial conducted at the University of Texas MD Anderson Cancer Center and the Mayo Clinic in Phoenix, Arizona, enrolled 62 patients with advanced biliary tract cancers between April 14, 2015, and April 24, 2017. INTERVENTIONS: Patients initially received gemcitabine, 1000 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 125 mg/m2, on days 1 and 8 of 21-day cycles. Owing to hematologic adverse events among the first 32 patients enrolled, these starting doses were reduced to 800, 25, and 100 mg/m2, respectively, for the remaining 28 patients. MAIN OUTCOMES AND MEASURES: The primary trial end point was investigator-assessed progression-free survival in the intention-to-treat population. RESULTS: Of 60 patients who started treatment, the mean (SD) age was 58.4 (11.0) years, 38 (63%) had intrahepatic cholangiocarcinoma, 9 (15%) had extrahepatic cholangiocarcinoma, 13 (22%) had gallbladder cancer, 47 (78%) had metastatic disease, and 13 (22%) had locally advanced disease. Median follow-up was 12.2 (95% CI, 9.4-19.4) months, and median progression-free survival was 11.8 (95% CI, 6.0 to 15.6) months. The partial response rate was 45%, and the disease control rate was 84%. Median overall survival was 19.2 months (95% CI, 13.2 months to not estimable). Patients in the safety population (n = 57) received a median of 6 (interquartile range, 3-11) cycles of treatment; 26 patients (46%) remained on their starting dose throughout the trial. Grade 3 or higher adverse events occurred in 58% of patients, and 9 patients (16%) withdrew owing to adverse events. Neutropenia was the most common grade 3 or higher adverse event, occurring in 19 patients (33%) overall. Post hoc analyses showed that treatment efficacy was not significantly associated with starting dose, tumor type, or disease status and that tolerability was improved with reduced- vs high-dose treatment. CONCLUSIONS AND RELEVANCE: Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs those reported for historical controls treated with gemcitabine-cisplatin alone. These findings will be tested in a phase 3 randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02392637.

Neuroendocrine Tumors and Lanreotide Depot: Clinical Considerations and Nurse and Patient Preferences.

BACKGROUND: Somatostatin analogs (SSAs) are a mainstay therapy for the treatment of carcinoid syndrome associated with neuroendocrine tumors (NETs). They are effective for a range of gastroenteropancreatic NETs (GEP-NETs). Lanreotide depot (Somatuline®) is an SSA that is approved for the treatment of GEP-NETs to improve progression-free survival (PFS). OBJECTIVES: The article reviews the efficacy, safety, and administration of lanreotide depot and relates those attributes to considerations and preferences of oncology nurses and their patients. METHODS: A review of the literature on the use of lanreotide for the treatment of NETs and carcinoid syndrome was conducted. In addition, the literature on drug delivery and routes of administration was surveyed to provide context for comparative studies related to clinical and patient preferences. FINDINGS: Lanreotide depot prolongs PFS and is well tolerated by patients who expressed satisfaction in the ability to control symptoms related to carcinoid syndrome. Nurses cited several benefits to using lanreotide depot in the clinical setting, including more time saved to address other patient care issues. Attributes of lanreotide depot-including its efficacy, safety and tolerability, dosing and administration, and cost-may contribute to healthcare decisions regarding the treatment and management of NETs.

Long-term care planning and preferences among Japanese American baby boomers: Comparison with non-Japanese Americans.

AIMS: Nikkei (Japanese American) communities are known to be forerunners for building culturally sensitive long-term care (LTC) services and programs. Existing literature highlights evolving cultural shifts among Nikkei communities as well as the baby boomers from the previous aging cohort. The present study's primary purpose was to examine Japanese American (JA) boomers' perceptions about their LTC planning compared with their non-JA counterparts. JA's residential and care preferences were also examined. METHODS: The study applied survey methodology with a total of 499 "boomers" (age 51-71 years) in the state of Washington. Data obtained from JA (n = 264) were compared with the data from non-JA Washingtonians (non-JA, n = 235). Data from an additional subset of questions asking JA's preferences for retirement/LTC facilities were also analyzed. RESULTS: The findings showed similarities and differences between the two groups. No group differences were found with regard to caregiving experiences, exposure to LTC, expectation of requiring future LTC or physical proximity to their adult children. JA boomers, however, showed more knowledge about LTC-related facts, stronger preference to avoid becoming dependent on their families and a higher rate of LTC insurance purchases. JA boomers ranked higher preferences on culturally universal elements (e.g. transportation services, Internet access) for their retirement and LTC facilities over Japanese cultural-specific elements. JA boomers also preferred to reside with a mixture of racial/ethnic residents. CONCLUSIONS: The present study suggests that the LTC industry including JA communities should accommodate boomers' retirement plans and preferences with a multicultural selection of services and settings. Geriatr Gerontol Int 2016; 16: 1074-1084.

Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma.

TRIAL REGISTRY: Clinicaltrials.gov #NCT01180959. BACKGROUND: Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. METHODS: For this single-arm, Phase II study, we recruited patients with Child-Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0-2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. RESULTS: A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months - not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%-59%), median time to progression was 3.9 months (95% CI: 2.0-8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3-15.5 months). Grade 3-4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). CONCLUSION: Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.

Suppression of hath1 gene expression directly regulated by hes1 via notch signaling is associated with goblet cell depletion in ulcerative colitis.

BACKGROUND: The transcription factor Atoh1/Hath1 plays crucial roles in the differentiation program of human intestinal epithelium cells (IECs). Although previous studies have indicated that the Notch signal suppresses the differentiation program of IEC, the mechanism by which it does so remains unknown. This study shows that the undifferentiated state is maintained by the suppression of the Hath1 gene in human intestine. METHODS: To assess the effect of Notch signaling, doxycycline-induced expression of Notch intracellular domain (NICD) and Hes1 cells were generated in LS174T. Hath1 gene expression was analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Hath1 promoter region targeted by HES1 was determined by both reporter analysis and ChIP assay. Expression of Hath1 protein in ulcerative colitis (UC) was examined by immunohistochemistry. RESULTS: Hath1 mRNA expression was increased by Notch signal inhibition. However, Hath1 expression was suppressed by ectopic HES1 expression alone even under Notch signal inhibition. Suppression of the Hath1 gene by Hes1, which binds to the 5' promoter region of Hath1, resulted in suppression of the phenotypic gene expression for goblet cells. In UC, the cooperation of aberrant expression of HES1 and the disappearance of caudal type homeobox 2 (CDX2) caused Hath1 suppression, resulting in goblet cell depletion. CONCLUSIONS: The present study suggests that Hes1 is essential for Hath1 gene suppression via Notch signaling. Moreover, the suppression of Hath1 is associated with goblet cell depletion in UC. Understanding the regulation of goblet cell depletion may lead to the development of new therapy for UC.

Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4.

BACKGROUND: Double balloon endoscopy (DBE) enables the observation and collection of viable specimens from the entire intestine, thereby allowing more detailed investigation of how the structure and function of the human small intestine are regulated. The present study aimed to elucidate the regulation of cell formation in the human small intestine using biopsy specimens collected from an entire individual small intestine by DBE. METHODS: The expression and the localization of representative genes for the differentiation program were analyzed in the entire small intestine of 10 patients. The functional correlation between Hath1 and Klf4 was analyzed in an intestinal cell line by using a Tet-On system. RESULTS: In longitudinal cell formation in the small intestine, it was shown that goblet cells, but not Paneth cells, increased toward the ileum in each individual small intestine. Immunohistochemistry showed that Hath1-expressing cells migrated from the base of the crypt to the top of the villi in the terminal ileum, while Klf4-expressing cells migrated from the top of the villus, resulting in the colocalization of Hath1 and Klf4 in the terminal ileum. Coexpression of Hath1 and Klf4 upregulated the expression of phenotypic genes for goblet cells following the downregulation of those for Paneth cells. CONCLUSIONS: Using mapping biopsy by DBE, we have demonstrated, for the first time, the molecular basis of the villus structure in the entire human small intestine in vivo. The present study showed that longitudinal cell formation was regulated by the colocalization of Hath1 and Klf4 that converted Paneth cell differentiation into goblet cell differentiation.

Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma.

PURPOSE: The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. PATIENTS AND METHODS: Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. RESULTS: The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). CONCLUSION: The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Attitudes toward older adults: a reexamination of two major scales.

Two studies were conducted to reexamine the psychometric properties of two major scales measuring attitudes toward older adults. The Kogan Attitudes Toward Old People Scale (Kogan OP Scale; Kogan, 1961b) was administered to a sample of 512 college students in Study One. The refined version (Polizzi & Millikin, 2002) of the Aging Semantic Differential (ASD; Rosencranz & McNeivin, 1969) using an attitudinal target, older adults, was evaluated in Study Two with a sample of 785 college students. Overall, the refined ASD using a nongender and age-specific attitudinal target, older adults, was found to be more psychometrically promising than the Kogan OP Scale. Much refinement is needed for the Kogan OP Scale because of a major flaw associated with OP+ and OP subscales. The refined ASD using older adults as the attitudinal target is a potentially practical tool in gerontological and geriatric fields with future clarification of its factor structure. Strengths and shortcomings of these scales are discussed based on psychometric features. Implications for future studies are discussed.