Use of calcium channel blockers and risk of breast cancer among women aged 55 years and older: a nationwide population-based cohort study.

This retrospective cohort study was aimed to compare the incidence of breast cancer among women aged ≥55 who received calcium channel blockers and angiotensin converting enzyme inhibitors/angiotensin II receptor blockers. We used the 2002-2015 Health and Welfare Database in Taiwan. Women 55 years and older who initiated antihypertensive treatment were included. Breast cancer risk for patients receiving calcium channel blockers was compared to those receiving angiotensin converting enzyme inhibitors/angiotensin II receptor blockers. Cox proportional hazards models were used to generate adjusted hazard ratios for breast cancer. We found that the risk of breast cancer was similar between calcium channel blockers users and angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (adjusted hazard ratio [aHR] and 95% CI = 1.03 [0.80 to 1.34]). No significant risk increase was observed in the stratified analysis by dihydropyridine (aHR = 1.02 [0.78 to 1.33]) and non-dihydropyridine calcium channel blockers (aHR = 1.23 [0.48 to 3.20]). No difference in the risk of breast cancer associated with calcium channel blockers exposure was observed in patients who used hormone replacement therapy (aHR = 1.02 [0.29 to 3.58]). The risk for breast cancer was observed to be significantly lower in patients receiving calcium channel blockers than in those receiving angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at a treatment duration of 5 or more years (aHR = 0.57 [0.33 to 0.98]). In conclusion, the risk for breast cancer is similar for calcium channel blockers and angiotensin converting enzyme inhibitors/angiotensin II receptor blocker users in an Asian population.

A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy.

BACKGROUND: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. METHODS: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. RESULTS: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment. CONCLUSIONS: Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity.

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

Application of the U.S. Food and Drug Administration's Sentinel Routine Querying Tools to the Taiwan Sentinel Data Model-formatted National Health Insurance Research Database.

The U.S. Food and Drug Administration's Sentinel System is a leading distributed data network for drug safety surveillance in the world. The National Health Insurance Research Database (NHIRD) in Taiwan was converted into the Taiwan Sentinel Data Model (TSDM) based on the Sentinel Common Data Model (SCDM) version 6.0.2. The goal of this study was to investigate the feasibility of applying the same study designs, analytic choices, and analytic tools as used by the U.S. Sentinel System to examine the same drug-outcome associations in the TSDM-formatted NHIRD. Four known drug-outcome associations previously examined by the U.S. Sentinel System were selected as the use cases: (1) use of angiotensin-converting enzyme inhibitors (ACEIs) and risk of angioedema, (2) use of warfarin and risk of gastrointestinal bleeding, (3) use of oral clindamycin and risk of Clostridioides difficile infection (CDI), and (4) use of glyburide and risk of serious hypoglycemia. We followed the same study designs and analytic choices used by the U.S. Sentinel System and applied the Sentinel Routine Querying Tools to answer the same study questions within the TSDM-formatted NHIRD. The results showed that ACEIs were associated with a non-significant increase in risk of angioedema compared to beta-blockers (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.89-1.64); warfarin was associated with a higher risk of gastrointestinal bleeding compared to statins (HR: 1.72; 1.50-1.98); glyburide was associated with an increased risk of hypoglycemia compared to glipizide (HR: 1.61, 1.30-2.00). We were unable to evaluate the association between oral clindamycin and risk of CDI due to the low event number. Our study demonstrated that it was feasible to directly apply the publicly available Sentinel Routine Querying Tools within the TSDM-formatted NHIRD. However, sources of heterogeneity other than design and analytic differences should be carefully considered when comparing the results between the two systems.

Reliability and Validity of a Chinese Version of the Cohen-Mansfield Agitation Inventory-Short Form in Assessing Agitated Behavior.

BACKGROUND: Patients with dementia often present agitated behaviors. The Cohen-Mansfield Agitation Inventory-short form (CMAI-SF) is one of the most widely used instruments to evaluate agitated behaviors that affect patients' quality of life and impose burden on caregivers. However, there is no simplified Chinese version of the CMAI-SF (C-CMAI-SF) in clinical settings. PURPOSE: This study aimed to develop a Chinese version of the C-CMAI-SF and examine its validity and reliability. METHODS: This cross-sectional study included three phases. In Phase I, the original CMAI-SF was translated to Chinese. In Phase II, experts were invited to examine the content validity index (CVI). Phase III was conducted to test the validity and reliability of the C-CMAI-SF. RESULTS: The scale showed good validity and reliability with a scale-level CVI of 0.89, Cronbach's alpha (measure of internal consistency) of 0.874, and test-retest correlation coefficient of 0.902 (for 257 individuals). Using factor analysis, three factors were identified. Regarding concurrent validity, the C-CMAI-SF score was correlated with the Neuropsychiatric Inventory (agitation aggression subscale) and the Cornell Scale for Depression in Dementia (agitation subscale). CONCLUSIONS: The study demonstrated that the C-CMAI-SF is a valid and reliable instrument for evaluating agitated behaviors in people with dementia. RELEVANCE TO CLINICAL PRACTICE: The C-CMAI-SF is an easy and quick tool used to identify and evaluate agitated behaviors in busy clinical settings.

Continuity and Completeness of Electronic Health Record Data for Patients Treated With Oral Hypoglycemic Agents: Findings From Healthcare Delivery Systems in Taiwan.

Objective: To evaluate the continuity and completeness of electronic health record (EHR) data, and the concordance of select clinical outcomes and baseline comorbidities between EHR and linked claims data, from three healthcare delivery systems in Taiwan. Methods: We identified oral hypoglycemic agent (OHA) users from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD), which was linked to the National Health Insurance Research Database (NHIRD), from June 2011 to December 2016. A secondary evaluation involved two additional EHR databases. We created consecutive 90-day periods before and after the first recorded OHA prescription and defined patients as having continuous EHR data if there was at least one encounter or prescription in a 90-day interval. EHR data completeness was measured by dividing the number of encounters in the NTUH-iMD by the number of encounters in the NHIRD. We assessed the concordance between EHR and claims data on three clinical outcomes (cardiovascular events, nephropathy-related events, and heart failure admission). We used individual comorbidities that comprised the Charlson comorbidity index to examine the concordance of select baseline comorbidities between EHRs and claims. Results: We identified 39,268 OHA users in the NTUH-iMD. Thirty-one percent (n = 12,296) of these users contributed to the analysis that examined data continuity during the 6-month baseline and 24-month follow-up period; 31% (n = 3,845) of the 12,296 users had continuous data during this 30-month period and EHR data completeness was 52%. The concordance of major cardiovascular events, nephropathy-related events, and heart failure admission was moderate, with the NTU-iMD capturing 49-55% of the outcome events recorded in the NHIRD. The concordance of comorbidities was considerably different between the NTUH-iMD and NHIRD, with an absolute standardized difference >0.1 for most comorbidities examined. Across the three EHR databases studied, 29-55% of the OHA users had continuous records during the 6-month baseline and 24-month follow-up period. Conclusion: EHR data continuity and data completeness may be suboptimal. A thorough evaluation of data continuity and completeness is recommended before conducting clinical and translational research using EHR data in Taiwan.

Effect of ICD-9-CM to ICD-10-CM coding system transition on identification of common conditions: An interrupted time series analysis.

PURPOSE: To evaluate the effect of diagnostic coding system transition on the identification of common conditions recorded in Taiwan's national claims database. METHODS: Using the National Health Insurance Research Database, we estimated the 3-month prevalence of recorded diagnosis of 32 conditions based on the ICD-9-CM codes in 2014-2015 and the ICD-10-CM codes in 2016-2017. Two algorithms were assessed for ICD-10-CM: validated ICD-10 codes in the literature and codes translated from ICD-9-CM using an established mapping algorithm. We used segmented regression analysis on time-series data to examine changes in the 3-month prevalence (both level and trend) before and after the ICD-10-CM implementation. RESULTS: Significant changes in the level were found in 19 and 11 conditions when using the ICD-10 codes from the literature and mapping algorithm, respectively. The conditions with inconsistent levels by both of the algorithms were valvular heart disease, peripheral vascular disease, mild liver disease, moderate to severe liver disease, metastatic cancer, rheumatoid arthritis and collagen vascular diseases, coagulopathy, blood loss anemia, deficiency anemia, alcohol abuse, and psychosis. Nine conditions had significant changes in the trend when using the ICD-10 codes from the literature or mapping algorithm. CONCLUSIONS: Less than half of the 32 conditions studied had a smooth transition between the ICD-9-CM and ICD-10-CM coding systems. Researchers should pay attention to the conditions where the coding definitions result in inconsistent time series estimates.

Building an active medical product safety surveillance system in Taiwan: Adaptation of the U.S. Sentinel System common data model structure to the National Health Insurance Research Database in Taiwan.

PURPOSE: Using real-world data to support regulatory decision has become a global movement. However, a robust platform for active surveillance of medical product safety has not been established in Taiwan. METHODS: Following the common data model structure of the U.S. Food and Drug Administration's Sentinel System, we built the Taiwan Sentinel Data Model (TSDM) using the National Health Insurance Research Database with longitudinal claims data from 23 million individuals, linked death and cause of death data from a national registry, and linked electronic health record data from a delivery system. We examined the conversion of the TSDM using the Sentinel Data Quality Review and Characterization Programs in a sample of sex- and age-stratified cohort of 3 million individuals. RESULTS: The TSDM fulfilled the requirements of data quality assurance. Only about 6% of sex and 0.0007% of birth year were missing, and <0.001% of date data had illogical values. CONCLUSIONS: The TSDM-converted database could be a valuable data resource for domestic pharmacovigilance analysis in Taiwan and cross-country evaluation.

Genome-wide DNA methylation analysis using MethylCap-seq in canine high-grade B-cell lymphoma.

DNA methylation is a comprehensively studied epigenetic modification and plays crucial roles in cancer development. In the present study, MethylCap-seq was used to characterize the genome-wide DNA methylation patterns in canine high-grade B-cell lymphoma (cHGBL). Canine methylated DNA fragments were captured and the MEDIUM-HIGH and LOW fraction of methylated DNA was obtained based on variation in CpG methylation density. In the MEDIUM-HIGH and LOW fraction, 2144 and 1987 cHGBL-specific hypermethylated genes, respectively, were identified. Functional analysis highlighted pathways strongly related to oncogenesis. The relevant signaling pathways associated with neuronal system were also revealed, echoing recent novel findings that neurogenesis plays key roles in tumor establishment. In addition, 14 genes were hypermethylated in all the cHGBL cases but not in the healthy dogs. These genes might be potential signatures for tracing cHGBL, and some of them have been reported to play roles in various types of cancers. Further, the distinct methylation pattern of cHGBL showed a concordance with the clinical outcome, suggesting that aberrant epigenetic changes may influence tumor behavior. In summary, our study characterized genome-wide DNA methylation patterns using MethylCap-seq in cHGBL; the findings suggest that specific DNA hypermethylation holds promise for dissecting tumorigenesis and uncovering biomarkers for monitoring the progression of cHGBL.

Oral short-acting antihypertensive medications and the occurrence of stroke: a nationwide case-crossover study.

The purpose of the study was to clarify whether short-acting antihypertensives are associated with the occurrence of ischemic stroke and intracerebral hemorrhage (ICH). This was a retrospective case-crossover study using the Taiwan National Health Insurance Research Database. We identified all adult patients hospitalized with a primary diagnosis of ischemic stroke or ICH between January 2005 and December 2013. For each case, short-term and long-term exposure to short-acting antihypertensives, including nifedipine, labetalol and captopril, during the case vs. control periods were compared, and odd ratios (ORs) and 95% confidence intervals (CIs) for ischemic stroke or ICH were calculated with adjustment for confounders. Among 272785 ischemic stroke and 77798 ICH patients, the mean age was 77.8 ± 14.3 years and 70.8 ± 16.6 years, respectively. The short-term use of the three short-acting antihypertensives were all associated with an increase in the incidence of ischemic stroke (nifedipine: OR 4.51, 95% CIs 3.99-5.11; labetalol: OR 2.07; 95% CIs 1.71-2.51; captopril: OR 1.98, 95% CIs 1.72-2.29) and ICH (nifedipine: OR 2.98, 95% CIs 2.30-3.84; labetalol: OR 2.37; 95% CIs 1.66-3.39; captopril: OR 2.48; 95% CIs 1.69-3.63). The long-term use of short-acting nifedipine for 30 days was associated with a modest increase in the risk for ischemic stroke (OR 1.86; 95% CIs 1.42-2.45). Overall, the short-term use of short-acting antihypertensives is associated with a modest increase in the incidence of stroke, and short-acting nifedipine is linked to a substantial rise in the incidence of ischemic stroke. The long-term use of short-acting nifedipine was also related to an increased incidence of ischemic stroke. Physicians should be cautious of prescribing these short-acting antihypertensives.

Time trends in first admission rates for schizophrenia and other psychotic disorders in Taiwan, 1998-2007: a 10-year population-based cohort study.

PURPOSE: To examine the trend in annual first admission rates for psychotic disorders as a whole as well as individual psychotic disorders in Taiwan from 1998 to 2007, and influences of age, sex, and geographic region on the trend. METHOD: Using the inpatient claims records in the National Health Insurance Research Database, we estimated the yearly first admission rates for schizophrenia and other psychotic disorders, including voluntary (1998-2007) and involuntary (2004-2007) admissions. Both narrow and broad definitions of psychotic disorders were examined. RESULTS: While involuntary first admission rates were stable, a crescendo-decrescendo change in voluntary first admission rates for psychotic disorders was observed, peaking in 2001. The increase from 1998 to 2001 was closely associated with health insurance expansion. Before 2001, the voluntary first admission rates in males aged 15-24 were underestimated as military personnel records were not included in the database. From 2001 to 2007, voluntary first admissions for psychotic disorders decreased 38%; the decrease could not be accounted for by the mild diagnostic shifts away from schizophrenia to affective psychosis or substance-induced psychosis. During the entire observation period, first admission rates for schizophrenia decreased 48%, while affective psychosis increased 84%. Gender disparities in the first admission rates gradually diminished, but geographic disparities persisted. CONCLUSIONS: First admission rates for psychosis significantly reduced in Taiwan between 1998 and 2007, mainly driven by the reduced hospitalization risk for schizophrenia. Special attention should be paid to the increased hospitalization for other types of psychotic disorders (especially affective psychosis) and the unresolved geographic disparities.

Risk of Flood-Related Diseases of Eyes, Skin and Gastrointestinal Tract in Taiwan: A Retrospective Cohort Study.

Floods are known to cause serious environmental damage and health impacts. Studies on flood-related diseases have been primarily on individual events, and limited evidence could be drawn on potential health impacts from floods using large population data. This study used reimbursement records of one million people of the Taiwan National Health Insurance program to compare incident diseases of the eyes, skin and gastrointestinal (GI) tract associated with floods. Incidence rates for the selected diseases were calculated according to outpatient/emergency visit data. The incidence rates were evaluated by flood status: in 10 days before floods, during floods and within 10 days after the floods receded. Outpatient/emergency visit rates for the eye, skin and GI tract diseases were highest after floods and lowest during floods. Results from multivariate Poisson regression analyses showed that, when compared with the incidence in 10 days before floods, the incidence rate ratios (IRR) of diseases within 10 days after floods were 1.15 (95% confidence interval (CI) = 1.10-1.20) for eyes, 1.08 (95% C.I. = 1.05-1.10) for skin, and 1.11 (95% CI = 1.08-1.14) for GI tract, after controlling for covariates. All risks increased with ambient temperature. V-shaped trends were found between age and eye diseases, and between age and GI tract diseases. In contrast, the risk of skin diseases increased with age. In conclusion, more diseases of eyes, skin and GI tract could be diagnosed after the flood.

Predicting Inpatient Readmission and Outpatient Admission in Elderly: A Population-Based Cohort Study.

Recognizing potentially avoidable hospital readmission and admissions are important health care quality issues. We develop prediction models for inpatient readmission and outpatient admission to hospitals for older adults In the retrospective cohort study with 2 million sampling file of the National Health Insurance Research Database in Taiwan, older adults (aged ≥65 y/o) with a first admission in 2008 were enrolled in the inpatient cohort (N = 39,156). The outpatient cohort included subjects who had ≥1 outpatient visit in 2008 (N = 178,286). Each cohort was split into derivation (3/4) and validation (1/4) data set. Primary outcome of the inpatient cohort: 30-day readmission from the date of discharge. The outpatient cohort included hospital admissions within the 1-year follow-up period. Candidate risk factors include demographics, comorbidities, and previous health care utilizations. Series of logistic regression models were applied with area under the receiver operating curves (AUCs) to identify the best model. Roughly 1 of 7 (14.6%) of the inpatients was readmitted within 30 days, and 1 of 5 (19.1%) of the outpatient cohort was admitted within 1 year. Age, education, use of home health care, and selected comorbidities (e.g., cancer with metastasis) were included in the final model. The AUC of the inpatient readmission model was 0.655 (95% confidence interval [CI] 0.646-0.664) and outpatient admission model was 0.642 (95% CI 0.639-0.646). Predictive performance was maintained in both validation data sets. The goodness-to-fit model demonstrated good calibration in both groups. We developed and validated practical clinical prediction models for inpatient readmission and outpatient admissions for general older adults with indicators easily obtained from an administrative data set.

Impact of universal health coverage on urban-rural inequity in psychiatric service utilisation for patients with first admission for psychosis: a 10-year nationwide population-based study in Taiwan.

OBJECTIVE: To examine the disparities in psychiatric service utilisation over a 10-year period for patients with first admission for psychosis in relation to urban-rural residence following the implementation of universal health coverage in Taiwan. DESIGN: Population-based retrospective cohort study. SETTING: Taiwan's National Health Insurance Research Database, which has a population coverage rate of over 99% and contains all medical claim records of a nationwide cohort of patients with at least one psychiatric admission between 1996 and 2007. PARTICIPANTS: 69,690 patients aged 15-59 years with first admission between 1998 and 2007 for any psychotic disorder. MAIN EXPOSURE MEASURE: Patients' urban-rural residence at first admissions. MAIN OUTCOME MEASURES: Absolute and relative inequality indexes of the following quality indicators after discharge from the first admission: all-cause psychiatric readmission at 2 and 4 years, dropout of psychiatric outpatient service at 30 days, and emergency department (ED) treat-and-release encounter at 30 days. RESULTS: Between 1998 and 2007, the 4-year readmission rate decreased from 65% to 58%, the 30-day dropout rate decreased from 18% to 15%, and the 30-day ED encounter rate increased from 8% to 10%. Risk of readmission has significantly decreased in rural and urban patients, but at a slower speed for the rural patients (p=0.026). The adjusted HR of readmission in rural versus urban patients has increased from 1.00 (95% CI 0.96 to 1.04) in 1998-2000 to 1.08 (95% CI 1.03 to 1.12) in 2005-2007, indicating a mild widening of the urban-rural gap. Urban-rural differences in 30-day dropout and ED encounter rates have been stationary over time. CONCLUSIONS: The universal health coverage in Taiwan did not narrow urban-rural inequity of psychiatric service utilisation in patients with psychosis. Therefore, other policy interventions on resource allocation, service delivery and quality of care are needed to improve the outcome of rural-dwelling patients with psychosis.

The experiences of family members in the year following the diagnosis of a child or adolescent with cancer: a qualitative systematic review.

BACKGROUND: Research shows that it is stressful for family members when a child or an adolescent within the family unit is diagnosed with cancer and this stress continues over the course of the year after the diagnosis. Qualitative studies have been conducted aimed at exploring parental, siblings' and other family members' experiences when facing health-illness transition-related stress during the first year after the child is diagnosed with cancer. This study integrates the research findings of relevant existing qualitative studies on this topic in order to provide empirical evidence-based suggestions for clinical care. OBJECTIVES: This study intent is to obtain an understanding of the family members' experiences over the course of the following year after learning that a child or adolescent within their family unit has been diagnosed with cancer. TYPES OF PARTICIPANTS: The participants of interest are family members of a child or adolescent with cancer who verbally describe the whole experience and/or report on the impact of the diagnosis and disease on their lives. In this systematic review, there were no restrictions on the type, severity and prognosis of cancer. Studies investigating the experiences of the family of a child or adolescent with cancer that were reported verbally and the opinions of others external to the family (e.g. nurses) were excluded from the review. PHENOMENA OF INTEREST: The phenomena of interest were the self-reported experiences over the course of the following year of family members of a child or adolescent with cancer and the impact on the whole family of the child or adolescent receiving a cancer diagnosis. The settings included acute care, home and community settings with any cultural context. Research on other phenomena, such as experiences related to social support intervention for the family, the long-term coping experience of the family, the bereavement experiences of children with cancer, the experiences of a child or adolescent with cancer and experiences more than one year after the diagnosis was excluded from the review. Types of studies: This review considered studies that used qualitative methods to examine the experiences of families of a child or adolescent with newly diagnosed cancer; these included but were not limited to designs such as qualitative research, phenomenology, hermeneutic phenomenology, grounded theory, ethnography, action research, focus groups and narrative research. The search was limited to studies published in English or Chinese because the reviewers were fluent in both of these languages. SEARCH STRATEGY: The search strategy sought to find both published and unpublished studies. CINAHL, PUBMED, ProQuest Dissertations and Theses and Chinese electronic periodical services were used to search for articles. METHODOLOGICAL QUALITY: Each paper was assessed independently by two reviewers for methodological quality. The Joanna Briggs Institute Qualitative Assessment and Review Instrument was used to appraise the methodological quality of the articles. Any disagreements that arose between the reviewers were resolved through discussion, or via a third reviewer. DATA EXTRACTION: Qualitative data were extracted from papers for inclusion in the review using the standardized data extraction tool from JBI-QARI. DATA SYNTHESIS: Qualitative research findings were extracted and pooled using JBI-QARI. RESULTS: A total of eight qualitative papers were included in the review (two grounded theory, four phenomenology and two qualitative inquiries). Five syntheses were derived: (1) family loss and the turmoil that surrounds the diagnosis of cancer; (2) a sense of courage and hope for mutual responsibility inspired by the changes in circumstances; (3) family support enhancing family members' resilience; (4) health professional-patient communication that provide a deeper understanding of the illness and their own situations; and (5) a positive attitude towards the illness and planning for the future. CONCLUSIONS: The research findings should help health professionals understand the nature of the experiences of family members of a child or adolescent with cancer. It is critical to assess the family member's level of preparedness in the face of the psychological stress associated with the potential loss of their healthy child. Health professionals should enhance family coping strategies in order to promote normal family life. This can be done by inspiring positive attitudes and empowerment aimed at caring for the child and helping the family to build the necessary health-related communication capacities in order to clarify the child's condition. IMPLICATIONS FOR PRACTICE: Clinical guideline suggestions for health professionals working with families of children or adolescent diagnosed with cancer within the first year following the diagnosis were identified. Health professionals must listen to and accept the emotions of shock, anger and loss by the family members who are facing the potential loss of their healthy child together with the upheaval in their lives and disruptions to their plans for the future. Health professionals should be encouraged to provide clear information to the whole family in relation to the treatment plan and caring strategies for the child. Nurses should provide family members with strategies to help with the normalization of their life and a return to their previous pre-cancer lifestyle. The medical team should exhibit professionalism and skills when treating the cancer in order to enhance the child's and his/her family members' trust and sense of safety in the medical care environment. Encouraging the family members of children with cancer to develop positive thinking and to plan for their future life should be a priority of the nursing care plan.

Water outage increases the risk of gastroenteritis and eyes and skin diseases.

BACKGROUND: The present study used insurance claims data to investigate infections associated with short-term water outage because of constructions or pipe breaks. METHODS: The present study used medical claims of one million insured persons for 2004-2006. We estimated incidences of gastroenteritis and eye and skin complaints for 10 days before, during, and after 10 days of water supply restriction for outpatient visits and for emergency and in-patient care combined. RESULTS: There was an increase in medical services for these complaints in outpatient visits because of water outages. Poisson regression analyses showed that increased risks of medical services were significant for gastroenteritis (relative risk [RR] 1.31, 95% confidence interval [CI] 1.26-1.37), skin disease (RR 1.36, 95% CI 1.30-1.42), and eye disease patients (RR 1.34, 95% CI 1.26-1.44). Similar risks were observed during 10-day lag periods. Compared with those in cool days, risks of medical services are higher when average daily temperature is above 30 °C for gastroenteritis (RR 12.1, 95% CI 6.17-23.7), skin diseases (RR 4.48, 95% CI 2.29-8.78), and eye diseases (RR 40.3, 95% CI 7.23-224). CONCLUSION: We suggest promoting personal hygiene education during water supply shortages, particularly during the warm months.

Tyrosine phosphorylation of growth factor receptor-bound protein-7 by focal adhesion kinase in the regulation of cell migration, proliferation, and tumorigenesis.

We have previously reported that growth factor receptor-bound protein-7 (Grb7), an Src-homology 2 (SH2)-containing adaptor protein, enables interaction with focal adhesion kinase (FAK) to regulate cell migration in response to integrin activation. To further elucidate the signaling events mediated by FAK*Grb7 complexes in promoting cell migration and other cellular functions, we firstly examined the phosphorylated tyrosine site(s) of Grb7 by FAK using an in vivo mutagenesis. We found that FAK was capable of phosphorylating at least 2 of 12 tyrosine residues within Grb7, Tyr-188 and Tyr-338. Moreover, mutations converting the identified Tyr to Phe inhibited integrin-dependent cell migration as well as impaired cell proliferation but not survival compared with the wild-type control. Interestingly, the above inhibitory effects caused by the tyrosine phosphorylation-deficient mutants are probably attributed to their down-regulation of phospho-Tyr-397 of FAK, thereby implying a mechanism by competing with wild-type Grb7 for binding to FAK. Consequently, these tyrosine phosphorylation-deficient mutants evidently altered the phospho-Tyr-118 of paxillin and phosphorylation of ERK1/2 but less on phospho-Ser-473 of AKT, implying their involvement in the FAK*Grb7-mediated cellular functions. Additionally, we also illustrated that the formation of FAK*Grb7 complexes and Grb7 phosphorylation by FAK in an integrin-dependent manner were essential for cell migration, proliferation and anchorage-independent growth in A431 epidermal carcinoma cells, indicating the importance of FAK*Grb7 complexes in tumorigenesis. Our data provide a better understanding on the signal transduction event for FAK*Grb7-mediated cellular functions as well as to shed light on a potential therapeutic in cancers.