Incidence, severity, and temporal development of oral complications in pediatric allogeneic hematopoietic stem cell transplant patients - a multicenter study.

PURPOSE: Oral mucositis is a common complication for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and causes pain and difficulties in functions like eating and swallowing, resulting in lower quality of life and greater need of treatment with opioids and parenteral nutrition. This prospective multicenter study focused on pediatric recipients of HSCT in the neutropenic phase concerning oral complications, timing, severity, and patient experience. METHODS: The cohort comprised 68 patients, median age 11.1 years (IQR 6.3) receiving allogeneic HSCT at three clinical sites. Medical records were retrieved for therapy regimens, concomitant medications, oral and dental history, and subjective oral complaints. Calibrated dentists conducted an oral and dental investigation before HSCT. After HSCT graft infusion, study personnel made bedside assessments and patients filled out a questionnaire once or twice a week until neutrophil engraftment. RESULTS: We followed 63 patients through the neutropenic phase until engraftment. 50% developed oral mucositis of grades 2-4. Peak severity occurred at 8-11 days after stem cell infusion. Altogether, 87% had subjective oral complaints. The temporal distribution of adverse events is similar to the development of oral mucositis. The most bothersome symptoms were blisters and oral ulcerations, including mucositis; 40% reported severe pain and major impact on activities of daily living despite continuous use of opioids. CONCLUSION: This study highlights the burden of oral complications and their negative effect on the health and quality of life of HSCT recipients.

Does information on age-related fertility decline and fertility policies affect university students' family and career expectations? Evidence from a randomized controlled trial.

BACKGROUND: Past research shows that young adults have poor knowledge of age-related fertility decline and that the provision of information can improve fertility knowledge. We provide university students with information on age-related fertility and fertility-related policies and investigate whether the provision of such information affects their family formation and career expectations. METHODS: A three-armed randomized controlled trial was conducted online in Singapore between September and October 2021. A total of 1000 undergraduate students were recruited through campus advertisements to complete a 30- to 45-minute online survey, which randomly exposed participants to one of three informational brochures on age-related fertility decline, fertility policies, or diabetes (control group). Participants answered questions on family formation and career expectations both before and after the information intervention. Analysis of covariance was used to assess the effects of the information intervention. RESULTS: Exposure to age-related fertility information resulted in significant reductions in the ideal age at first childbirth, significant increases in the expected probability of marriage before age 30, and (among female participants) significant increases in the expected likelihood of undergoing social egg-freezing. No difference existed in child-number ideals, educational aspirations, and income expectations between groups after exposure. No difference existed between the fertility policy information group and the control group after exposure in any of the outcomes of interest. CONCLUSIONS: Information on age-related fertility decline brought forward university students' expected timing of childbearing and marriage without reducing their educational and career expectations. The provision of fertility information at early ages, such as during university, can help correct widespread inaccurate beliefs about fertility and promote realistic family formation planning without adversely affecting educational and career goals. TRIAL REGISTRATION: ClinicalTrials.gov.

Sibling Spillovers: Having an Academically Successful Older Sibling May be More Important for Children in Disadvantaged Families.

This paper examines causal sibling spillover effects among students from different family backgrounds in elementary and middle school. Family backgrounds are captured by race, household structure, mothers' educational attainment, and school poverty. Exploiting discontinuities in school starting age created by North Carolina school-entry laws, we adopt a quasi-experimental approach and compare test scores of public school students whose older siblings were born shortly before and after the school-entry cutoff date. We find that individuals whose older siblings were born shortly after the school-entry cutoff date have significantly higher test scores in middle school, and that this positive spillover effect is particularly strong in disadvantaged families. We estimate that the spillover effect accounts for approximately one third of observed statistical associations in test scores between siblings, and the magnitude is much larger for disadvantaged families. Our results suggest that spillover effects from older to younger siblings may lead to greater divergence in academic outcomes and economic inequality between families.

Improving visual outcomes in patients with rare paediatric eye diseases.

Introduction: Rare paediatric eye diseases (RPEDs) threaten both vision and life. Recently, rare diseases were recognised as a global public health agenda, with children specified as a priority in the World Health Organization's VISION 2020 against avoidable visual loss. Method: We conducted a review through a query of online databases (PubMed, Embase and Cochrane Library). Articles related to RPEDs were selected based on relevance by 2 authors, with any disagreements adjudicated by the third author. Results: We synthesise the current state of knowledge regarding RPEDs, barriers to their care, and recommendations for the future. RPEDs often result in significant visual loss, profoundly impacting the way children comprehend and participate in the world. These diseases may also reduce life expectancy and even be life-threatening. Barriers to the care of RPEDs include an unclear definition of "rare diseases", missed or delayed diagnosis, inadequate knowledge and expertise in management, and challenging research environments. Conclusion: Our findings provide an update on the diagnosis and management of RPEDs, which is of relevance to ophthalmologists, paediatricians, healthcare policymakers and social workers. We propose supportive policies and adequate resource allocation to these diseases, comprehensive and patient-centred care, alongside improved education and training, enhanced research capabilities and continued collaboration across institutions.

Changes in Frequency and Patterns of Marital Sexual Activity During COVID-19: Evidence From Longitudinal Data Prior to, During and After Lockdown in Singapore.

BACKGROUND: The literature suggests that the pandemic has affected sexual activity and sexual desire around the world, potentially due to increased levels of stress, movement restrictions under lockdown conditions, and changes in relationship quality. AIM: To investigate changes in frequency and patterns of marital sexual activity and the role of potential factors underlying these changes, during and after COVID-19 lockdown. METHODS: This longitudinal study followed 409 heterosexual married female participants who completed a baseline survey in April-July 2018 and biweekly online surveys over the next 14 weeks; an online survey in May 2020 during the lockdown in Singapore; and an online survey in June 2020 after the lockdown was lifted. Participants were recruited in 2018 using street intercept and screened for inclusion and exclusion criteria. Logistic fixed-effects models were used to test for changes in frequency and patterns of marital sexual activity and assess underlying factors. Pseudo-design-based sample weights were applied. OUTCOMES: The 2018 in-person baseline survey collected information on demographic characteristics and ideal frequency of marital sex, while follow-up online questionnaires in May-June 2020 included items on exact dates of marital sexual activity of previous weeks; stress and fatigue levels; both spouses' stay-at-home statuses during lockdown; and marital satisfaction. RESULTS: 409 heterosexual married women were included in this study. Compared to pre-pandemic levels, the proportion of participants not having marital sex within a week remained stable while weekly sexual frequency increased, with more evenly distributed sexual activity on weekdays and weekends. Stress, fatigue, and marital satisfaction levels predicted probability of non-activity and sexual frequency. CLINICAL TRANSLATION: The increase in weekly sexual frequency has implications for sexual and reproductive health, including sexual satisfaction and prevalence of infertility and low birth weight associated with waiting time to pregnancy. STRENGTHS & LIMITATIONS: The longitudinal nature of the dataset provides unique insights into differences in frequency of marital sexual activity during compared to before the pandemic. Unlike previous studies, detailed data on exact dates of sexual activity allow for detection of differences in sexual activity by day of the week. However, dates of sexual activity were recorded retrospectively and may contain recall errors. Data were collected only from wives and hence dates of marital sexual activities were not cross-validated with husbands. CONCLUSION: Results point to more active and flexible marital sex lives during the pandemic, with effects that persisted after the lockdown ended. Tan PL. Changes in Frequency and Patterns of Marital Sexual Activity During COVID-19: Evidence From Longitudinal Data Prior to, During and After Lockdown in Singapore. J Sex Med 2022;19:188-200.

Fortunes of Dragons: Cohort size effects on life outcomes.

This paper examines the long-term effects of birth cohort size on life outcomes. Using administrative data from Singapore, we study the outcomes of large birth cohorts created by the Chinese superstitious practice of zodiac birth timing, where parents prefer to give birth in the year of the Dragon. This practice is followed exclusively by the Chinese majority, with no similar patterns detected among non-Chinese minorities, allowing us to differentiate cohort size effects from confounding year-of-birth effects. Despite government efforts to increase public educational resources for these cohorts, Chinese Dragons earn lower incomes and are less likely to gain admission to national universities. There is also evidence of negative externalities on non-practising populations who happen to enter the labour market at the same time as Chinese Dragons. Our analysis suggests that the adverse life outcomes are not due to selection, but rather reflect the aggregate resource implications of birth cohort size.Supplementary material is available for this article at: https://doi.org/10.1080/00324728.2020.1864458.

Stress, Fatigue, and Sexual Spontaneity Among Married Couples in a High-Stress Society: Evidence from Sex Diary Data from Singapore.

This paper investigates the associations between stress and fatigue and sexual spontaneity among heterosexual married couples in Singapore, a high-income society with high work performance expectations and long working hours. Data on self-reported menstrual dates, sexual activity within the marriage, and stress and fatigue levels were collected from 657 married women aged 25-34 years through biweekly online diaries over 14 weeks. Using a two-way fixed effects logistic model which controlled for time-invariant individual fixed effects and menstrual cycle fixed effects, the paper tests three hypotheses: (1) sexual activity is significantly lower on weekdays compared to weekends and public holidays, (2) sexual activity is significantly lower during periods when women reported higher stress and fatigue, and (3) stress and fatigue are more predictive of sexual activity during weekdays than during weekends. Frequencies of marital sexual intercourse during the diary keeping period were 3.69 and 2.55 per 30 days among women aged 25-29 and 30-34 years, respectively, much lower than ideal frequencies of 6.40 and 5.23. Consistent with all three hypotheses, there was a strong positive weekend effect and a weak but positive public holiday effect, and strong negative effects of both stress and fatigue, especially during weekdays. There was no evidence of compensatory sex on weekends to make up for hectic workweeks. Increased support for work-life balance can contribute to more spontaneous marital sex lives and may reduce underachievement of ideals for sexual intimacy and childbearing in Singapore.

Dual Burdens of Care: "Sandwiched Couples" in East Asia.

OBJECTIVE: To estimate proportions of married couples aged 30 to 59 years who face simultaneous demands from elderly parents and children in China, Japan, Korea, and Taiwan, and the effects on couples' life and marital satisfaction. METHOD: Using data from the 2006 East Asian Social Survey, proportions of sandwiched couples were estimated using three definitions: co-residence, co-residence or nearby residence, and co-residence or frequent provision of financial/physical assistance. Logistic regression models were used to assess the effects on life and marital satisfaction. RESULTS: Three-generational co-residence is more common in Taiwan and Japan (24.3% and 21.4%), whereas co-residence or provision for both generations is higher in Taiwan and Korea (53.7% and 44.5%). The strain of being sandwiched is associated with lower life and marital satisfaction only among women. DISCUSSION: Intergenerational transfers of care play a major role in elderly support in East Asia but take a toll on the well-being of married women.

Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study.

Purpose Although IKZF1 deletion ( IKZF1del) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10-7), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1-negative disease, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.

Risk Factors for Mortality in Asian Children Admitted to the Paediatric Intensive Care Unit after Haematopoietic Stem Cell Transplantation.

INTRODUCTION: This study aimed to investigate the risk factors associated with mortality in haematopoietic stem cell transplant (HSCT) patients admitted to our paediatric intensive care unit (PICU) over an 8-year period. MATERIALS AND METHODS: A retrospective chart review was conducted of all HSCT patients requiring PICU admission at our centre (a tertiary care university hospital in Singapore) from January 2002 to December 2010. Chief outcome measures were survival at the time of PICU discharge and survival at 6 months after initial PICU admission. RESULTS: Ninety-eight patients underwent HSCT during this period; 18 patients (18%) required 24 PICU admissions post-HSCT. The overall survival to PICU discharge was 62.5%. Of those who survived discharge from the PICU, 33% died within 6 months of discharge. Non-survivors to PICU discharge had a higher incidence of sepsis (89% vs 33%, P = 0.013) and organ failure as compared to survivors (cardiovascular failure 100% vs 20%, P = 0.0003; respiratory failure 89% vs 20%, P = 0.002; and renal failure 44% vs 7%, P = 0.047). Mortality rates were higher in patients requiring mechanical ventilation (70% vs 14%, P = 0.010) and inotropic support (70% vs 14%, P = 0.010). Mortality in all patients with renal failure requiring haemodialysis (n = 4) was 100%. Presence of 3 or more organ failures was associated with 80% mortality (P = 0.003). CONCLUSION: Sepsis, multiple organ failure and the need for mechanical ventilation, inotropes and especially haemodialysis were associated with increased risk of mortality in our cohort of HSCT patients.

Second Malignant Neoplasms in Childhood Cancer Survivors Treated in a Tertiary Paediatric Oncology Centre.

Introduction: One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods: A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results: We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years (P <0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies. Conclusion: This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Cutaneous Emboli of Invasive Basidiomycosis in a Child With Aplastic Anemia.

Invasive fungal diseases are a significant cause of mortality among the immunocompromised. This report documents an unusual case of disseminated fungal infection in a child with severe aplastic anemia. The offending fungus, a Basidiomycete, is rarely known to cause human infections. The patient presented acutely with multiple purpuric skin lesions in various parts of the body. The skin biopsy revealed septated fungal hyphae embolized within small dermal blood vessels. Molecular sequencing indicated Earliella scabrosa as the likely organism. The clinical course of the infection was inexorable despite systemic antifungal treatment, resulting in mortality. The literature of human infections due to Basidiomycetes, the usefulness of histopathology in the early diagnosis of the infection, and possible treatment options are discussed.

Case report: An unusual presentation of oral acute graft-versus-host-disease in a haploidentical hematopoietic stem cell transplant recipient.

Oral acute graft-versus-host disease (aGVHD) is a significant sequelae of allogeneic hematopoietic stem cell transplantation (HSCT). Presently, transplant physicians have to diagnose GVHD based on clinical judgment by interpreting available clinical and relevant laboratory findings. As such, characterization of diagnostic and distinctive clinical signs and symptoms of GVHD is essential for diagnosis and grading. The oral features of aGVHD have been reported infrequently and remain ill defined, unlike in oral chronic GVHD. The report describes an atypical and painful presentation of oral aGVHD in a 15-year-old boy, 16 days after haploidentical HSCT, who presented with swollen lips, herpetiform ulcerations, and erythematous fungiform papilla.

A Case for "Reverse One-Child" Policies in Japan and South Korea? Examining the Link between Education Costs and Lowest-Low Fertility.

Household spending on children's pre-tertiary education is exceptionally high in Japan and South Korea, and has been cited as a cause of low fertility. Previous research attributes this high spending to a cultural emphasis on education in East Asian countries. In this paper, we argue that institutional factors, namely higher education and labor market systems, play an important role in reinforcing the pressure on parents to invest in their children's education. We review evidence showing that graduating from a prestigious university has very high economic and social returns in Japan and South Korea, and examine the implications for fertility within the framework of quantity-quality models. Finally, we put forward 'reverse one-child' policies that directly address the unintended consequences of these institutional factors on fertility. These policies have the additional virtues of having very low fiscal requirements and reducing social inequality.

Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children and young adults has similar molecular signature to extranodal nasal natural killer/T-cell lymphoma but shows distinctive stem cell-like phenotype.

We performed gene expression profiling in Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative disorder in children and young adults (TNKLPDC) in order to understand the molecular pathways deregulated in this disease and compared it with nasal-type NK/T-cell lymphoma (NKTL). The molecular and phenotypic signature of TNKLPDC is similar to NKTL, with overexpression of p53, survivin and EZH2. Down-regulation of EZH2 in TNKLPDC cell lines led to an increase in apoptosis and decrease in tumor viability, suggesting that EZH2 may be important for the survival of TNKLPDC cells and hence potentially a useful therapeutic target. Notably, our gene expression profiling revealed a distinctive enrichment of stem cell related genes in TNKLPDC compared to NKTL. This was validated by a significantly higher expression of aldehyde dehydrogenase 1 (ALDH1) in TNKLPDC cell lines compared to NKTL cell lines. The novel discovery of cancer stem cell properties in TNKLPDC has potential therapeutic implications in this group of disorders.

Prognostic implication of morphology, cyclinE2 and proliferation in EBV-associated T/NK lymphoproliferative disease in non-immunocompromised hosts.

BACKGROUND: EBV-associated T/NK-cell lymphoproliferative diseases (TNKLPD) is a rare spectrum of disease that occurs more commonly in Asia, and Central and South America. It commonly affects children and young adults and is an aggressive disease that is poorly understood with no known biologic markers that can predict prognosis. The systemic form of TNKLPD includes chronic active EBV infection of T/NK type, aggressive NK cell leukemia and systemic EBV + T-cell lymphoproliferative disease of childhood. METHODS: In this study, we analyse the clinicopathologic and genetic features of 22 cases of systemic TNKLPD in non-immunocompromised patients, including chronic active EBV infection of T/NK cell type and systemic EBV + T-cell lymphoproliferative disease of childhood. We also performed gene expression profiling in a subset of cases to identify markers that may be of prognostic relevance and validated our results using immunohistochemistry. RESULTS: The median age is 14.9 years and two of our 22 cases occurring in patients older than 30 years. Fifteen of 17 cases (88%) with adequate data were of T-cell origin. Eleven of 22 cases revealed polymorphic cellular infiltrate (P-group) while the rest showed monomorphic lymphoid infiltrate (M-group). We found a significant difference in survival between P-group vs M-group patients with median survival not yet reached in P-group, and 1 month in M-group (p = 0.0001), suggesting a role for morphology in predicting patient outcome. We also performed gene expression profiling in a subset of patients and compared the genes differentially expressed between P-group and M-group cases to identify markers of prognostic value. We identified cyclin E2 gene and protein to be differentially expressed between patients with good outcome (P-group, median expression 8%) and poor outcome (M-group, median expression 42%) (p = 0.0005). In addition, the upregulation of cyclin E2 protein in M-group cases correlated with a higher Ki67 proliferation rate (Pearson correlation r = 0.73, p = 0.0006) detected by immunohistochemistry. High cyclin E2 expression was also significantly associated with shorter survival (p = 0.0002). CONCLUSION: Our data suggests the potential role of monomorphic morphology, high cyclin E2 and Ki67 expression as adverse prognostic factors for TNKLPD.