Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0-18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996-December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008-2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996-2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1-RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008-2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008-2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008-2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents' use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG-ALL-2002 study.

BACKGROUND: To eliminate cranial irradiation (CrRT)-related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)-directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: This study compared the treatment outcomes of patients overall and patients with a non-CNS-1 status (CNS-2, CNS-3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG-ALL-2002 protocol by the introduction of the modification (era 1 [2002-2008] with CrRT and era 2 [2009-2012] with delayed first TIT and no CrRT). RESULTS: There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5-year event-free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non-CNS-1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5-year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2. CONCLUSIONS: The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non-CNS-1 status.

[Narrative Pedagogy in Nursing Education: The Essence of Clinical Nursing Process Recording].

BACKGROUND: Clinical nursing process recording (CNPR) has been shown to be an effective tool for facilitating student-centered teaching and learning in nursing education. Yet, the essence and process of this tool have yet to be sufficiently explored and clarified. PURPOSE: To explore the essence of CNPR in the contexts of clinical teaching and learning. METHODS: Reflective analysis was used as the phenomenological approach to analyze the qualitative data, which were transcribed from the oral responses of the six participants who were attending the Clinical Nursing Education Forum. A total of five sessions of the Clinical Nursing Education Forums were conducted. The content of the Clinical Nursing Education Forums consisted of a series of 12 narrative writings of CNPR that were written by a senior student and read and commented on by the student's clinical instructor. RESULTS: Three groups of the essence and process of clinical teaching and learning were inductively identified as: (a) mobilizing autonomous, self-directed learning behavior from self-writing and re-storying; (b) establishing the student-instructor dialogical relationship from mutual localization; and (c) co-creating a learning environment in education and in clinical practice. CONCLUSIONS: When used as an interactive teaching and learning tool, CNPR promotes mutual understanding by re-locating the self in the coexisting roles of student nurse, instructor, and patient in a series of nursing care situations. This re-location facilitates students' self-directed learning, enhances the abilities of asking question, waiting for and accompany with the instructor; and promotes the self-care capabilities of patients.

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation.

BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.

Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Virological characteristics of cervical cancers carrying pure episomal form of HPV16 genome.

OBJECTIVE: Many studies on integration have reported conflicting results regarding the role of HPV integration in cervical cancer. We hypothesized that high viral load and disruption of E2 gene associated with integration of HPV were not the only pathway leading to cancer development. METHODS: This study analysed the viral load and integration status of HPV16, measured the HPV16 E6/E7 mRNA transcript levels, delineated the E2 and LCR sequence variation, and determined the methylation status of two E2 binding sites. RESULTS: The results showed that viral load was not associated with the physical status of HPV genome. Levels of the three E6/E7 mRNA transcripts in invasive cervical cancers containing purely episomal viral genome were found to be similar to those containing integrated viral genome, suggesting that cancers containing episomal viral genome were also mediated by an up-regulated E6/E7 mRNA expression, and more importantly, did not depend on integration and disruption of the E2 gene. CONCLUSIONS: The alternative mechanism that up-regulated the expression of E6 and E7 in invasive cancers harbouring episomal viral genome was likely to be a consequence of methylation of the two E2 binding sites located at the promoter region of HPV16. These observations are in line with the hypothesis that HPV integration was not the only mechanism leading to the development of cervical cancer.

Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China.

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.

Relationships between stress, coping and depressive symptoms among overseas university preparatory Chinese students: a cross-sectional study.

BACKGROUND: Mental health problems in young people are an important public health issue. Students leaving their hometown and family at a young age to pursue better educational opportunities overseas are confronted with life adjustment stress, which in turn affects their mental health and academic performance. This study aimed to examine the relationships among stress, coping strategies, and depressive symptoms using the stress coping framework in overseas Chinese university preparatory students in Taiwan. METHODS: A cross-sectional study was conducted at an overseas Chinese university preparatory institute in Taiwan. Of enrolled overseas Chinese university preparatory students at 2009, 756 completed a structured questionnaire measuring stress, strategies for coping with it, and the Center for Epidemiologic Studies Depression Scale. RESULTS: High levels of stress significantly predicted the adoption of active, problem-focused coping strategies (R(2) = 0.13, p < .01) and passive, emotion-focused coping strategies (R(2) = 0.24, p < .01). Acceptable CFI, SRMR, and RMSEA values from the structural equation modeling analysis demonstrated that the model satisfactorily fits the stress coping framework, after active coping strategies were eliminated from the model. Results from the Sobel test revealed that passive coping strategies mediated the relation between stress and depressive symptoms (z = 8.06, p < .001). CONCLUSION: Our study results suggested that stress is associated with coping strategies and depressive symptoms and passive strategies mediate the relation between stress and depressive symptoms in overseas Chinese university preparatory students.

Comparison of the effects of episiotomy and no episiotomy on pain, urinary incontinence, and sexual function 3 months postpartum: a prospective follow-up study.

BACKGROUND: The episiotomy rate has declined worldwide but remains high in several countries such as Taiwan. The effects of episiotomy on women's health should be a constant concern. Few data are available on the effect of episiotomy by validated measures. OBJECTIVE: The present study examined the effect of episiotomy on pain, urinary incontinence, and sexual function up to 3 months postpartum. DESIGN, SETTING AND PARTICIPANTS: A prospective follow-up study of 243 women who completed the Taiwanese versions of the Short Form McGill Pain Questionnaire, International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form, Female Sexual Function Index, and a demographic questionnaire after vaginal delivery in a Taiwanese medical center. METHODS: Differences between those who did and did not have an episiotomy were tested using ANCOVA, adjusting for age, parity, newborn weight, and vacuum delivery. The reliability and validity of the measuring instruments were assessed using Cronbach's α coefficient and factor analysis. RESULTS: Women who delivered without an episiotomy had significantly lower perineal pain scores at weeks 1, 2 and 6 postpartum compared to women who had an episiotomy (p=0.0065, 0.0391, 0.0497, respectively). Women in the no-episiotomy group had significantly lower non-localized pain scores at week 2 postpartum compared to women in the episiotomy group (p=0.0438). The mean urinary incontinence score was significantly higher in the episiotomy group 3 months postpartum (p=0.0293). No significant difference in sexual function score was found between groups. CONCLUSIONS: The results indicate that episiotomy increased pain at weeks 1, 2 and 6 postpartum, and urinary incontinence at 3 months postpartum. Awareness of the relationship between episiotomy and women's health will help health care professionals develop policy and promote the application of restrictive episiotomy.

Age distribution of human papillomavirus infection and cervical neoplasia reflects caveats of cervical screening policies.

Although a second age-related peak of human papillomavirus (HPV) infection is observed in many populations, it does not seem to have any impact on cervical screening policies. We examined the age-specific prevalence of HPV infection among 2,604 women enrolled for cervical screening and correlated the age at diagnosis of 2,491 cervical intraepithelial neoplasia Grade 2/3 (CIN2/3) lesions and 801 invasive cervical cancers (ICC). Two peaks of HPV infection were detected at 26-30 and 46-50 years, respectively. The first infection peak was followed by a CIN2/3 peak and an ICC peak at 5-15 and 15 years later, respectively. The second infection peak was followed by an ICC peak 20 years later, but strikingly no CIN2/3 peak was detected in between and thus eliminated an opportunity of treating the lesions at preinvasive stages. The most plausible explanation is that women at the expected second CIN2/3 peak (50-65 years) are not having Pap smears under the current opportunistic screening program. Furthermore, women of this age may have physiological retraction of the transformation zone, and CIN lesions may remain undetected if an adequate Pap smear sample is not obtained. To combat this problem, the screening program in Hong Kong needs to focus on women aged 50 years and older and a mop-up screening up to 75 years is necessary. Bimodal peaks of HPV infection and cervical cancer are seen in many countries and the analysis of population-specific age distribution of CIN2/3 should be an integral exercise in evaluating the effectiveness of a screening program.

Transformation in self-identity amongst Taiwanese women in late pregnancy: a qualitative study.

BACKGROUND: In a culture transitioning between the traditions of old and modernity, the experience of pregnancy brings added challenges. Pregnant Taiwanese women in large cities are expected to modify their behavior in keeping with long-standing traditions that remain important to their families even if they themselves do not endorse the beliefs. To date, researchers have not examined the processes and the components of the transformation of self-identity during pregnancy under these cultural conditions. OBJECTIVES: To examine the transformation of self during pregnancy by women living in urban Taiwan at a time when modern ideas of women's roles and health care practices co-exist with traditional cultural beliefs on these issues. METHODS: This was a qualitative study using in-depth, open-ended interviews. Eighteen pregnant women receiving prenatal examinations at clinics located in a medical center in Taipei, Taiwan, participated in this study. Interview responses were analyzed using a phenomenological approach. RESULTS: Cultural and family expectations clearly influenced women's activities and their sense of self during pregnancy. Two themes were central to these experiences. The first, "constructing a new self in the context of cultural values," reflected the need for women to develop a response to the traditional beliefs, taboos, and public advice made very explicit in their lives during pregnancy. The second theme, "building a new body image from the past self," addresses how women's reactions to the traditional beliefs and public advice influenced the ways in which the women viewed themselves as pregnant individuals. CONCLUSIONS: Cultural factors and body image issues shape the transformation of self-identity during pregnancy for women living in a modernizing, yet culturally traditional, urban environment in Taiwan. Awareness of the impact that such cultural influences have on the psycho-social experience of pregnancy will help health professionals to better understand and respect the process of self-identity involved in moving toward motherhood, and thereby to provide a woman-centered model of care that is also culturally sensitive.

Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer.

The clinical value of viral load and integration testing for human papillomavirus (HPV) remains unclear. Data on HPV type 18 (HPV18) is limited. We examined the HPV18 viral load and integration status of 78 women with normal cervix or neoplasia. While the crude viral load appeared to increase with lesion severity, the association was not significant after normalization with sample cellularity. Unlike reports for HPV16, the amino-terminal 1 region of HPV18 E2 was most frequently (71.0%) disrupted, representing the best marker for integration. A substantial proportion (57.1%) of invasive cancers harbored only the episomal genome, thus jeopardizing the clinical value of integration testing. A large proportion (41.7%) of normal/low-grade lesions showed viral integration, suggesting that integration of HPV18 starts early and is unlikely to be a sole determinant for progression. Interpretation of viral load should take into account the form of HPV infection as single infections had significantly higher viral loads than coinfections (P = 0.046). More data generated from routinely collected samples are warranted to verify the clinical value of viral load and integration testing. Viral load quantitation for HPV18 is premature for clinical use at this stage.

Childbirth-related fatigue trajectories during labour.

AIM: This paper is a report on a study identifying trajectories of childbirth-related fatigue intensity changes over time and the influencing factors related to specific trajectory patterns. BACKGROUND: Childbirth is a period of time that encompasses considerable physiological and psychological fatigue, often having an adverse impact on women in labour. Empirical studies on this issue are scarce. How childbirth-related fatigue changes over time, and factors influencing fatigue development, remain unclear. METHOD: A prospective, correlational design with repeated measures was used. Data were collected by self-reported measures and laboratory analysis of blood specimens. From December 2004 to November 2005 a convenience sample of 209 low-risk pregnant Taiwanese women was followed throughout the labour process. Repeated measures of fatigue were analysed by using a semiparametric mixture model. Variables explaining trajectory class membership were identified by means of logistic regression. RESULTS: Two distinct trajectories of childbirth-related fatigue were identified: low intensity (30.8% of women) and high intensity (69.2% of women). Fatigue level of both classes intensified following labour. The fastest period of fatigue-increasing rate was in the active phase. After birth, fatigue levels in the high-fatigue intensity class remained high. Primiparas in the high-fatigue intensity class experienced significantly more anxiety and higher lactate concentration at admission than the low-intensity class. CONCLUSION: Caregivers should endeavour to prevent high levels of fatigue once women enter the labour phase. Women who present with high fatigue at onset of labour should be targeted for early intervention, especially in the period of rapid fatigue increase.

[The analysis and recommendation of the institutional respite care policy in Taiwan].

As the functionally impaired disabled elderly and the long-term care population has grown, concern about the physical, psychological and social demands facing primary caregivers has increased. An institutional respite care policy was adopted in Taiwan in 1998, but the rate of utilization of institutional care remains low. This article investigates the formative background, related circumstances and problems of respite care policy. The three dimensions of structure, process and outcome form the main framework for policy analysis. "Structure," includes demand and resources. "Process," includes health policy planning procedure, health administration and service delivery processes. "Outcome," covers service utilization, satisfaction, caregiver's well-being and care-receiver's institutionalization rate. In accordance with the results of the analysis the researchers propose recommendations about policy, practice, education and research, in the hope that these will be considered in relation to future modification and execution of respite care policy, in order to provide respite for suffering caregivers, and to carry out the ideal of aging in place.

Expression of placental leptin and leptin receptors in preeclampsia.

This study investigated the expression profile of placental leptin and leptin receptor isoforms in preeclampsia, using placental tissue from normal pregnancies that were matched in gestational age and birth weight as controls. A total of 29 cases of preeclampsia were studied by immunohistochemistry, including 16 severe and 13 mild preeclampsia cases. Reverse transcriptase-polymerase chain reaction (RT-PCR) was further performed using RNA extracted from frozen tissue (10 severe preeclampsia, 10 mild preeclampsia, and 20 normal third trimester placentas). In all tissue sections, immunostaining signal was shown in the cytoplasmic compartment of the trophoblastic cells. Both the severe and mild preeclampsia groups showed significantly higher immunostaining for leptin compared with normal controls (p < 0.05), but there was no significant difference between the severe and mild preeclampsia groups (p > 0.05). There was no significant difference in immunostaining for leptin receptor between both severe and mild preeclampsia compared with controls (p > 0.05). RT-PCR showed significantly higher levels of mRNA transcripts of leptin in severe preeclampsia (p < 0.05), but not mild preeclampsia (p > 0.05), compared with normal controls. No significant difference in expression of all the receptor isoforms was demonstrated between both severe and mild preeclampsia groups compared with controls (p > 0.05). In conclusion, we confirmed an up-regulated expression of leptin in placental tissue in preeclampsia. However, there was no difference in the expression of all leptin receptor isoforms in placental tissue between preeclamptic and normal pregnancies. The leptin signal probably does not play a major primary role in the pathogenesis of preeclampsia.

Intravenous leiomyomatosis: two cases with different routes of tumor extension.

Intravenous leiomyomatosis is a rare smooth muscle tumor. We report two cases of intravenous leiomyomatosis that grew along different routes of the venous system into the inferior vena cava and the right atrium. The different route of extension makes a difference in the ease of excision of tumor masses. Using MEDLINE together with the references in each publication, we identified all cases of intracardiac leiomyomatosis reported in the English literature in the period between 1980 and 2003 and performed a brief review on this potentially lethal disease entity.

Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers.

Loss of heterozygosity (LOH) at chromosome 3p21 is frequent in cervical cancers. The candidate tumor suppressor gene, RASSF1A located at 3p21.3, is found to be inactivated in several major human cancers, implicating its significance in carcinogenesis. We aimed to investigate the status of RASSF1A in cervical cancers. The mutation and methylation status of RASSF1A were analysed in 4 cervical cancer cell lines, 50 primary cervical cancers including 33 squamous cell carcinoma (SCC), 17 adenocarcinoma (AC) and 11 normal controls. The primary cancer samples were also detected for LOH at 3p21 and human papillomavirus (HPV). Hypermethylation of RASSF1A was detected in 30% of SCC, 12% of AC and in 1 of the 4 cancer cell lines but was absent in all normal cases. Methylation of the cancer cell line was associated with loss of gene expression, which was restored by demethylation. About 67% (8 of 12) of hypermethylated primary cancers showed concomitant LOH at 3p21. No somatic mutation was found in all primary cancer samples or cell lines but 2 cases showed germline polymorphism at codon 133. Oncogenic HPV DNAs were found in most cancer samples. No correlation was detected between RASSF1A-hypermethylation or LOH at 3p21 and age of patient, HPV genotype, tumor grade and stage. Hypermethylation of RASSF1A occurs in a subset of cervical cancers, among which concomitant LOH at 3p21 is common. The results supported that RASSF1A may be one of the cervical cancer-related tumor suppressor genes located at 3p21 regions.