Efficacy of oral corticosteroids for acute preschool wheeze: a systematic review and individual participant data meta-analysis of randomised clinical trials.

BACKGROUND: Oral corticosteroids are commonly used for acute preschool wheeze, although there is conflicting evidence of their benefit. We assessed the clinical efficacy of oral corticosteroids by means of a systematic review and individual participant data (IPD) meta-analysis. METHODS: In this systematic review with IPD meta-analysis, we systematically searched eight databases (PubMed, Ovid Embase, CINAHLplus, CENTRAL, ClinicalTrials.gov, EudraCT, EU Clinical Trials Register, WHO Clinical Trials Registry) for randomised clinical trials published from Jan 1, 1994, to June 30, 2020, comparing oral corticosteroids with placebo in children aged 12 to 71 months with acute preschool wheeze in any setting based on the Population, Intervention, Comparison, Outcomes framework. We contacted principal investigators of eligible studies to obtain deidentified individual patient data. The primary outcome was change in wheezing severity score (WSS). A key secondary outcome length of hospital stay. We also calculated a pooled estimate of six commonly reported adverse events in the follow-up period of IPD datasets. One-stage and two-stage meta-analyses employing a random-effects model were used. This study is registered with PROSPERO, CRD42020193958. FINDINGS: We identified 16 102 studies published between Jan 1, 1994, and June 30, 2020, from which there were 12 eligible trials after deduplication and screening. We obtained individual data from seven trials comprising 2172 children, with 1728 children in the eligible IPD age range; 853 (49·4%) received oral corticosteroids (544 [63·8%] male and 309 [36·2%] female) and 875 (50·6%) received placebo (583 [66·6%] male and 292 [33·4%] female). Compared with placebo, a greater change in WSS at 4 h was seen in the oral corticosteroids group (mean difference -0·31 [95% CI -0·38 to -0·24]; p=0·011) but not 12 h (-0·02 [-0·17 to 0·14]; p=0·68), with low heterogeneity between studies (I2=0%; τ2<0·001). Length of hospital stay was significantly reduced in the oral corticosteroids group (-3·18 h [-4·43 to -1·93]; p=0·0021; I2=0%; τ2<0·001). Subgroup analyses showed that this reduction was greatest in those with a history of wheezing or asthma (-4·54 h [-5·57 to -3·52]; pinteraction=0·0007). Adverse events were infrequently reported (four of seven datasets), but oral corticosteroids were associated with an increased risk of vomiting (odds ratio 2·27 [95% CI 0·87 to 5·88]; τ2<0·001). Most datasets (six of seven) had a low risk of bias. INTERPRETATION: Oral corticosteroids reduce WSS at 4 h and length of hospital stay in children with acute preschool wheeze. In those with a history of previous wheeze or asthma, oral corticosteroids provide a potentially clinically relevant effect on length of hospital stay. FUNDING: Asthma UK Centre for Applied Research.

Outdoor air pollution and near-fatal/fatal asthma attacks in children: A systematic review.

BACKGROUND: Globally, observational studies have demonstrated an association between high levels of air pollution and asthma attacks in children. It remains unclear whether and to what extent exposure may be associated with increased near-fatal/fatal attacks. OBJECTIVE: To systematically review the evidence for an association between ambient outdoor air pollution and fatal and/or near-fatal asthma (NFA). METHODS: Following Cochrane methodology, we searched MEDLINE, EMBASE, Web of Science, Scopus, and Open Grey electronic databases for studies reporting the association of fatal/NFA and air pollution (particulate matter [PM], sulfur dioxide, nitrogen dioxide, black carbon and ozone [O3]) in children. NFA was defined as requiring intensive care unit (ICU) management. RESULTS: Two reviewers independently screened 1358 papers. A total of 276 studies identified asthma attacks related to air pollution, 272 did not meet inclusion criteria after full-text review. Four observational studies described fatal/NFA, of which three addressed NFA. PM2.5 (per 12.5 µg/m3 increase) and O3 (per 22 ppb increase) were associated with NFA in one study (PM2.5, relative risk: 1.26, confidence interval [CI] [1.10-1.44]), O3 (1.19 [1.01-1.40]). PM10 was associated with ICU admission in the context of thunderstorm asthma. Elemental carbon was associated equally with NFA that did not require an ICU admission (p = 0.67). Studies of fatal asthma including children did not demarcate age within the analysis. CONCLUSIONS: Ozone and PM2.5 have been associated with NFA in children but synthesis is limited by the paucity of studies and methodological heterogeneity. Poor reporting of severities of asthma attacks hinders the assessment of whether outdoor air pollution is associated with an increased number of NFA/fatal attacks in children.

Menstrual and psychosocial characteristics associated with high-risk of premenstrual dysphoric disorder among university students: a cross-sectional study.

Up to 92 percent of Chinese women of reproductive age have pre-menstrual syndrome (PMS). The severe form of PMS (i.e. pre-menstrual dysphoric disorder [PMDD]) negatively affects women's everyday functioning and reproductive health. This study examined the relationships between menstrual, psychosocial characteristics and the risk of PMDD among young Chinese women. A cross-sectional online survey was conducted among Chinese university students in Hong Kong. Logistic regression was used to compute adjusted odds ratio (aOR) for the association of high-risk PMDD with menstrual and psychosocial characteristics. A total of 541 Chinese university students were recruited. Approximately 53 percent of female students were at high risk of developing PMDD. The high-risk PMDD group was significantly associated with a heavy volume of menstrual flow (aOR = 2.17, 95 percent CI 1.06-4.45), irregular menstrual cycle (1.72, 1.17-2.52), high dysmenorrhea (2.80, 1.95-4.04) and older ages of menarche (0.67, 0.45-0.98) in the menstrual characteristics. In the psychosocial characteristics, high-risk PMDD was significantly associated with symptoms of anxiety (2.19, 1.48-3.32) and depression (2.22, 1.48-3.32), high loneliness (1.94, 1.34-2.79) and low resilience (2.21, 1.52-3.23) levels. Additionally, resilience had a potential moderating effect on the associations between the high risk of PMDD and anxiety, depression and loneliness. The development and delivery of interventions that can enhance resilience and manage psychological distress would be beneficial for young Chinese women's reproductive health.

Impact of COVID-19 mitigations on anxiety and depression amongst university students: A systematic review and meta-analysis.

Background: While much research has addressed mental health concerns related to the coronavirus disease 2019 (COVID-19) pandemic, there remains a scarcity of studies specifically exploring the changes in anxiety and depression among university students before and after the implementation of COVID-19 mitigation measures. Methods: In this systematic review and meta-analysis, we searched databases including MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), ERIC (EBSCO), the WHO COVID-19 database, Scopus, and Science Citation Index (Web of Science) as of 15 February 2023. We included studies that used a validated tool to measure changes in anxiety or depression at two distinct time points - before (T1) and during (T2); during (T2) and after (T3); or before (T1) and after (T3) COVID-19 mitigation. The quality of studies was assessed using an adapted Joanna Briggs Institute Checklist for longitudinal studies. Utilising random-effects models, we synthesised changes in continuous outcomes as standardised mean difference (SMD) with 95% confidence interval (CI) and binary outcomes as risk difference (RD) with 95% CI. Results: In total, 15 studies were included in this review, with eight of moderate and seven of high quality. In most of the included studies (n = 13), the majority of participants were women. Eleven studies analysed mental health outcomes between T1 and T2 of COVID-19 mitigations. Continuous symptom changes were a minimal or small improvement for anxiety (SMD = -0.03, 95% CI = -0.24 to 0.19, I2 = 90%); but worsened for depression (SMD = 0.26, 95% CI = -0.01 to 0.62). However, the proportions of students reporting moderate-to-severe symptoms, defined by specific cut-offs, increased during COVID-19 mitigation measures for both anxiety (RD = 0.17, 95% CI = -0.04 to 0.38, I2 = 95%) and depression (RD = 0.12, 95% CI = 0.03 to 0.22, I2 = 72%). Sensitivity analyses, which distinguished between baseline periods based on awareness of COVID-19, demonstrated an exacerbation of both symptoms when comparing the period before the global awareness of the COVID-19 outbreak (before December 2019) with the period during the implementation of mitigation measures. Conclusions: Mental health outcomes, especially depressive symptoms, were observed to worsen in university students during COVID-19 mitigations. Despite considerable heterogeneity requiring careful interpretation of results, the impact of COVID-19 mitigations on mental health in university students is evident. Registration: PROSPERO (CRD42021266889).

Patient financial incentives to improve asthma management: a systematic review.

OBJECTIVES: The objectives of this systematic review are to identify studies that assess the effectiveness of patient-directed financial incentive interventions to improve asthma management behaviours, determine overall effectiveness of financial incentives, identify design characteristics of effective interventions and assess the impact on longer-term outcomes in the context of asthma. DESIGN: Systematic review with narrative synthesis. DATA SOURCES: Electronic databases (MEDLINE, Embase, Global Health, PsycINFO, CINAHL, PubMed and Web of Science) and grey literature sources (NHS Digital, CORE, ProQuest, Clinical Trials Register and EU Clinical Trials Register) were searched in November 2021 and updated March 2023. ELIGIBLITY CRITERIA: Eligible articles assessed financial incentives to improve asthma management behaviours (attendance at appointments, medication adherence, tobacco smoke/allergen exposure, inhaler technique and asthma education) for patients with asthma or parents/guardians of children with asthma. Eligible study design included randomised controlled, controlled or quasi-randomised trials and retrospective/prospective cohort, case-controlled or pilot/feasibility studies. SYNTHESIS: A narrative synthesis was conducted; eligible studies were grouped by asthma management behaviours and financial incentive framework domains. RESULTS: We identified 4268 articles; 8 met the inclusion criteria. The studies were from the USA (n=7) and the UK (n=1). Asthma management behaviours included attendance at appointments (n=4), reduction in smoke exposure (n=1) and medication adherence (n=3). Five studies demonstrated positive behaviour change, four of which were significant (attendance at appointments (n=3) showed significant differences between intervention and control: 73% and 49% in one study, 46.3% and 28.9% in another, and 35.7% and 18.9%, respectively; medication adherence (n=1) showed significant change from 80% during intervention to 33% post intervention). These four significant studies used 'positive gain', 'certain', 'fixed' financial incentives of smaller magnitude, given for 'all' instances of behaviour. CONCLUSION: There is some evidence that patient-directed financial incentives improve asthma management behaviours. However, in view of the wide heterogeneity in study design and measured outcomes, determining overall effectiveness was challenging. PROSPERO REGISTRATION NUMBER: CRD42021266679.

The benefits, challenges, and best practice for patient and public involvement in evidence synthesis: A systematic review and thematic synthesis.

INTRODUCTION: Despite the growing evidence on patient and public involvement (PPI) in health research, little emphasis has been placed on understanding its quality and appropriateness to evidence synthesis (ES) and systematic reviews (SR). This study aimed to synthesise qualitative evidence on the benefits, challenges, and best practices for PPI in ES/SR projects from the perspectives of patients/public and researchers. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, Cochrane Library and CINAHL Plus. We also searched relevant grey literature and conducted hand-searching to identify qualitative studies which report the benefits and challenges of PPI in individual ES/SR projects. Studies were independently screened by two reviewers for inclusion and appraised using the Joanna Briggs Institute's Qualitative Tool. Included studies were synthesised narratively using thematic synthesis. RESULTS: The literature search retrieved 9923 articles, of which eight studies were included in this review. Five themes on benefits emerged: two from patients'/public's perspective-gaining knowledge, and empowerment; and three from researchers' perspective-enhancing relevance, improving quality, and enhancing dissemination of findings. Six themes on challenges were identified: three from patients'/public's perspective-poor communication, time and low self-esteem; and three from researchers' perspective-balancing inputs and managing relations, time, and resources and training. Concerning recommendations for best practice, four themes emerged: provision of sufficient time and resources, developing a clear recruitment plan, provision of sufficient training and support, and the need to foster positive working relationships. CONCLUSION: Highlighting the benefits and challenges of PPI in ES/SR projects from different stakeholder perspectives is essential to understand the process and contextual factors and facilitate meaningful PPI in ES/SR projects. Future research should focus on the utilisation of existing frameworks (e.g., Authors and Consumers Together Impacting on eVidencE [ACTIVE] framework) by researchers to help describe and/or report the best approaches and methods for involving patients/public in ES/SRs projects. PATIENT AND PUBLIC CONTRIBUTION: This review received great contributions from a recognised PPI partner, the Chair of the Cochrane Consumer Network Executive, to inform the final stage of the review (i.e., interpretation, publication and dissemination of findings). The PPI partner has been included as an author of this review.

Re-analysis of ventilator-free days (VFD) in acute respiratory distress syndrome (ARDS) studies.

BACKGROUND: Over recent decades, improvements in healthcare have reduced mortality and morbidity rates in many conditions. This has resulted, in part, from the identification of effective interventions in randomised trials, and in conducting such trials, a composite outcome measure (COM) with multiple components will increase event rates, which allows study completion with a smaller sample size. In critical care research, the COM "ventilator-free days" (VFD) combines mortality and duration of mechanical ventilation (MV) into a single continuous measure, which can be analysed in a variety of ways. This study investigates the usefulness of Poisson and two-part Poisson models compared to t-distribution for the analysis of VFD. METHODS: Data from four studies (ALbuterol for the Treatment of ALI (ALTA), Early vs. Delayed Enteral Nutrition (EDEN), Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute Lung Injury (ALI) to reduce pulmonary dysfunction (HARP-2), Statins for Acutely Injured Lungs from Sepsis (SAILS)) were used for analysis, with the VFD results summarised using mean, standard deviation (SD), median, interquartile range (25th and 75th percentiles) and minimum and maximum values. The statistical analyses that are compared used the t-test, Poisson, zero-inflated Poisson (ZIP) and two-part Logit-Poisson hurdle models. The analyses were exploratory in nature, and the significance level for differences in the estimates was set to 0.05. RESULTS: In HARP-2, which compared simvastatin and placebo, the mean (SD) VFD for all patients was 12.0 (10.2), but this mean value did not represent the data distribution as it falls in a zone between two peaks, with the lowest frequency of occurrence. The mean (SD) VFD after excluding patients who died before day 28 and patients who did not achieve unassisted breathing were 15.9 (8.7) and 18.2 (6.6), respectively. The mean difference (95% CI) between the two groups was 1.1 (95% CI: 0.7 to 2.8; p = 0.20) based on an independent t-test. However, when the two-part hurdle model was used, the simvastatin arm had a significantly higher number of non-zero values compared to the placebo group, which indicated that more patients were alive and free of mechanical ventilation in the simvastatin group. Similarly, in ALTA, this model found that significantly more patients were alive and free of MV in the control group. In EDEN and SAILS, there was no significant difference between the control and intervention groups. CONCLUSION: Our analyses show that the t-test and Poisson model are not appropriate for bi-modal data (such as VFD) where there is a large number of zero events. The two-part hurdle model was the most promising approach. There is a need for future research to investigate other analysis techniques, such as two-part quantile regression and to determine the impact on sample size requirements for comparative effectiveness trials.

Risk of serious COVID-19 outcomes among adults and children with moderate-to-severe asthma: a systematic review and meta-analysis.

BACKGROUND: The Joint Committee on Vaccination and Immunisation in the United Kingdom requested an evidence synthesis to investigate the relationship between asthma and coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We conducted a systematic review and meta-analysis to summarise evidence on the risk of severe COVID-19 outcomes in people with uncontrolled asthma or markers of asthma severity. METHODS: High-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) were used as markers of asthma severity, following international or national asthma guidelines. Risk of bias was assessed using Joanna Briggs Institute tools. Adjusted point estimates were extracted for random-effects meta-analyses and subgroup analyses. RESULTS: After screening, 12 studies (11 in adults and one in children) met the eligibility criteria. Adults using high-dose ICS or OCS had a pooled adjusted hazard ratio (aHR) of 1.33 (95% CI 1.06-1.67, I2=0%) for hospitalisation and an aHR of 1.22 (95% CI 0.90-1.65, I2=70%) for mortality for COVID-19. We found insufficient evidence for associations between markers on COVID-19 mortality in the subgroup analyses. CONCLUSIONS: Adults with severe asthma are at increased risk of COVID-19 hospitalisation compared to nonusers. Our analysis highlighted the dearth of studies in children with asthma investigating serious COVID-19 outcomes.

Clinical features of COVID-19 for integration of COVID-19 into influenza surveillance: A systematic review.

Background: In November 2020, the World Health Organization (WHO) created interim guidance on how to integrate testing for SARS-CoV-2 into existing influenza surveillance systems. Influenza-like illness (ILI) and severe acute respiratory illness (SARI) case definitions have been used to specify the case definition of COVID-19 for surveillance purposes. This review aims to assess whether the common clinical features of COVID-19 have changed to the point that the criteria used to identify both COVID-19 and influenza in surveillance programs needs to be altered. Methods: A systematic review of reviews following PRISMA-P guidelines was conducted using the "COVID-19 evidence review" database from August 19, 2020, to August 19, 2021. Reviews providing pooled estimates of the prevalence of clinical features of COVID-19 within the general population, diagnosed by polymerase chain reaction or rapid diagnostic test, were included. These were critically appraised and sensitivity analysis was undertaken to examine potential causes of bias. Results: Fourteen reviews were identified, including three on adults only and three on children only. For all reviews, combined fever (median prevalence = 73.0%, IQR = 58.3-78.7) and cough (45.1%, IQR = 28.9-54.0) were the most common features. These were followed by loss of taste or smell (45.1%, IQR = 28.9-54.0), hypoxemia (33%, one review), fatigue (26.4%, IQR = 9.0-39.4) and expectoration (23.9%, IQR = 23.3-25.5). Fever and cough continued to be the most prevalent features for adults and children, with subsequent symptoms being similar for adults only. However, the pattern differed for children, with headache (34.3%, IQR = 18-50.7) and nasal congestion (20%, one review) being the third and fourth commonest symptoms. Conclusions: The prevalent features found in this recent review were the same as the ones identified at the beginning of the pandemic. Therefore, the current approach of using the ILI and SARI criteria which incorporate fever and cough will identify COVID-19 cases in addition to influenza. Interestingly, children may present with different features, as headaches and nasal congestion were more common in this group. Future research could examine this further and investigate whether symptomology changes with new variants of COVID-19.

Parietal and medial temporal lobe interactions in working memory goal-directed behavior.

Working memory is essential for the organization of goal-directed behavior, which involves multiple brain networks. The frontoparietal network has been proposed as a central node for the maintenance and manipulation of information. However, the exact contribution of the frontal and parietal lobes is still unclear as is that of the medial temporal lobe (MTL). Here, we investigated how the frontoparietal network and the MTL coordinate cognitive functions to control working memory in 12 participants, including five men, with medically intractable epilepsy. Participants performed a modified Sternberg working memory task during intracranial electroencephalography recording. The present working memory task was designed to test the different neural states of working memory subprocesses during memory maintenance and operation. First, we observed increased and sustained low-frequency (2-7 Hz) power in the frontal lobe and MTL, relative to baseline activity during the entire working memory task. Parietal alpha (8-13 Hz) power exhibited peak activity during memory operation. Finally, we found a positive correlation in the alpha band between the MTL and the parietal lobe during memory operation. These results indicate that as task demands become specific and goal-directed, the correlation between the MTL and the parietal lobe increases. This finding provides novel insight into the contribution of the MTL-parietal lobe network to voluntary control of working memory.

Synergy Through Integration of Wearable EEG and Virtual Reality for Mild Cognitive Impairment and Mild Dementia Screening.

Virtual reality (VR) technologies have shown promising potential in the early diagnosis of dementia by enabling accessible and regular assessment. However, previous VR studies were restricted to the analysis of behavioral responses, so information about degenerated brain dynamics could not be directly acquired. To address this issue, we provide a cognitive impairment (CI) screening tool based on a wearable EEG device integrated into a VR platform. Subjects were asked to use a hardware setup consisting of a frontal six-channel EEG device mounted on a VR device and to perform four cognitive tasks in VR. Behavioral response profiles and EEG features were extracted during the tasks, and classifiers were trained on extracted features to differentiate subjects with CI from healthy controls (HCs). Notably, the performance of the patient classification consistently improved when EEG characteristics measured during cognitive tasks were additionally included in feature attributes than when only the task scores or resting-state EEG features were used, suggesting that our protocol provides discriminative information for screening. These results propose that the integration of EEG devices into a VR framework could emerge as a powerful and synergistic strategy for constructing an easily accessible EEG-based CI screening tool.

Mobile Apps Leveraged in the COVID-19 Pandemic in East and South-East Asia: Review and Content Analysis.

BACKGROUND: The COVID-19 pandemic increased attention to digital tools to support governmental public health policies in East and South-East Asia. Mobile apps related to the COVID-19 pandemic continue to emerge and evolve with a wide variety of characteristics and functions. However, there is a paucity of studies evaluating such apps in this region, with most of the available studies conducted in the early days of the pandemic. OBJECTIVE: This study aimed to examine free apps developed or supported by governments in the East and South-East Asian region and highlight their key characteristics and functions. We also sought to interpret how the release dates of these apps were related to the commencement dates of other COVID-19 public health policies. METHODS: We systematically searched for apps in Apple App Store and Google Play Store and analyzed the contents of eligible apps. Mobile apps released or updated with COVID-19-related functions between March 1 and May 7, 2021, in Singapore, Taiwan, South Korea, China (mainland), Japan, Thailand, Hong Kong, Vietnam, Malaysia, Indonesia, and the Philippines were included. The CoronaNet Research Project database was also examined to determine the timeline of public health policy commencement dates in relation to the release dates of the included apps. We assessed each app's official website, media reports, and literature through content analysis. Descriptive statistics were used to summarize relevant information gathered from the mobile apps using RStudio. RESULTS: Of the 1943 mobile apps initially identified, 46 were eligible, with almost 70% of the apps being intended for the general public. Most apps were from Vietnam (n=9, 20%), followed by Malaysia, Singapore, and Thailand (n=6 each, 13%). Of note, most apps for quarantine monitoring (n=6, 13%) were mandatory for the target users or a population subset. The most common function was health monitoring (32/46, 70%), followed by raising public health awareness (19/46, 41%) through education and information dissemination. Other functions included monitoring quarantine (12/46, 26%), providing health resources (12/46, 26%). COVID-19 vaccination management functions began to appear in parallel with vaccine rollout (7/46, 15%). Regarding the timing of the introduction of mobile solutions, the majority of mobile apps emerged close to the commencement dates of other public health policies in the early stages of the pandemic between March and April 2020. CONCLUSIONS: In East and South-East Asia, most governments used mobile health apps as adjuncts to public health measures for tracking COVID-19 cases and delivering credible information. In addition, these apps have evolved by expanding their functions for COVID-19 vaccination.

Early assessment of response to induction therapy in acute myeloid leukemia using 18F-FLT PET/CT.

BACKGROUND: We evaluated the suitability of 18F-fluorodeoxythymidine (18F-FLT) positron emission tomography (PET)/computed tomography (CT) for assessment of the early response to induction therapy and its value for predicting clinical outcome in patients with acute myeloid leukemia (AML). Adult patients who had histologically confirmed AML and received induction therapy were enrolled. All patients underwent 18F-FLT PET/CT after completion of induction. PET/CT images were visually and quantitatively assessed. Cases with intensely increased bone marrow uptake in more than one third of the long bones and throughout the central skeleton were interpreted as PET-positive for resistant disease (RD). PET results were compared to the clinical response and outcome. RESULTS: In visual PET analysis of 10 eligible patients (7 male, 3 female; median age 58 years), 5 patients were interpreted as being PET-positive and 5 as PET-negative. Standardized uptake values were significantly different between PET-positive and PET-negative groups. Eight of 10 patients achieved clinical complete remission (CR)/CR with incomplete blood count recovery (CRi). Five CR/CRi patients had PET-negative findings, but 3 CR patients had PET-positive findings. Both of the RD patients had PET-positive findings. During follow-up, 2 CR patients with PET-positive findings relapsed, or were strongly suspected of relapse, 4 months after consolidation. CONCLUSION: 18F-FLT PET/CT after induction therapy showed good sensitivity and negative-predictive value for evaluating RD in patients with AML. This preliminary study suggests that 18F-FLT PET/CT may be valuable as a noninvasive tool for early assessment of the response to treatment and may provide prognostic value for survival in patients with AML.

Clinical impact of induction treatment modalities and optimal timing of radiotherapy for the treatment of limited-stage NK/T cell lymphoma.

This study retrospectively investigated the optimal timing of radiotherapy (RT) in patients with limited-stage extranodal NK/T-cell lymphoma (ENTKL). Among 158 patients with newly diagnosed stage I/II ENKTL, 61 patients were treated with sequential chemotherapy followed by radiotherapy (SCRT), 55 with concurrent chemoradiotherapy followed by non-anthracycline-based chemotherapy (CCRT/CT), and 42 with chemotherapy (CT) only. The 5-year overall survival (OS) rate did not differ between SCRT (77.7±5.5%) and CCRT/CT (68.9±6.8%; p=0.234). In the SCRT group, 18 patients (29.5%) relapsed within the RT field and 6 (9.8%) at systemic sites, while in the CCRT/CT group, 9 patients (16.4%) relapsed at the primary site and 14 (25.5%) at systemic sites. The 5-year cumulative incidence of relapse (CIR) at primary sites was 26.3% and 19.2% after SCRT and CCRT/CT (p=0.308), while the 5-year CIR of systemic sites was 8.7% and 26.5% after SCRT and CCRT/CT, respectively (p=0.010). In the multivariate analysis, NK/T-cell Prognostic Index score and CR achievement were the most important prognostic factors for survival. Although up-front RT had limitations in systemic disease control and was associated with an increased risk of systemic relapse during RT compared to SCRT, timing of RT did not significantly affect survival outcomes.

Long-Term Outcomes after Imatinib Mesylate Discontinuation in Chronic Myeloid Leukemia Patients with Undetectable Minimal Residual Disease.

BACKGROUND: Imatinib mesylate (IM) discontinuation is under active investigation in chronic myeloid leukemia-chronic phase (CML-CP) patients with undetectable minimal residual disease (UMRD). However, limited data exist on the long-term outcomes following IM discontinuation in patients treated with frontline IM therapy. METHODS: We consecutively enrolled patients with CML-CP who discontinued IM after achieving UMRD for ≥12 months between June 2009 and January 2013. RESULTS: Nineteen patients (8 male, 11 female) were included. After IM discontinuation, 14 patients (74%) lost UMRD after a median of 4.0 months. Of the 14 patients with molecular relapses, 12 (86%) relapsed within the first 9 months after IM discontinuation and 2 (14%) relapsed at 20.5 and 22.8 months, respectively. No molecular relapse was observed after 2 years of IM discontinuation. With a median follow-up of 58.1 months (range 23.0-66.5), the estimated UMRD persistence rate at 5 years was 23.7%. IM was readministered in all patients with molecular relapse, and 12 patients (86%) reachieved UMRD at a median of 5.3 months. A high-risk Sokal score, delayed UMRD achievement and short-term IM therapy were significantly associated with molecular relapse. CONCLUSION: These findings suggest that IM discontinuation in patients who achieved UMRD after frontline IM therapy resulted in favorable long-term outcomes in terms of safety and feasibility.

Importance-satisfaction analysis of street food sanitation and choice factor in Korea and Taiwan.

BACKGROUND/OBJECTIVES: The present study investigated Korean and Taiwan adults on the importance of and the satisfaction with street food sanitation and street food choice factor, in order to present management and improvement measures for street foods. SUBJECTS/METHODS: The present study conducted a survey on 400 randomly chosen adults (200 Korean, 200 Taiwanese). General characteristics, eating habits, street food intake frequency, and preference by type of street food of respondents were checked. Respondents' importance and satisfaction of street food hygiene and selection attributes were also measured. In order to test for the difference between groups, χ(2)-test and t-test were performed. ISA was also performed to analyze importance and satisfaction. RESULTS: Results showed that the importance of sanitation was significantly higher than satisfaction on all items in both Korea and Taiwan, and the satisfaction with sanitation was higher in Taiwan than in Korea. According to ISA results with street food sanitation, satisfaction was low while importance was high in both Korea and Taiwan. In terms of street food choice factor, importance scores were significantly higher than satisfaction scores on all items. In addition, satisfaction scores on all items except 'taste' were significantly higher in Taiwan than in Korea. CONCLUSIONS: A manual on sanitation management of street foods should be developed to change the knowledge and attitude toward sanitation by putting into practice a regularly conducted education. Considering the popularity of street foods and its potential as a tourism resource to easily publicize our food culture, thorough management measures should be prepared on sanitation so that safe street food culture should be created.

Clinical outcome and prognosis of patients with primary sinonasal tract diffuse large B-cell lymphoma treated with rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy: a study by the Consortium for Improving Survival of Lymphoma.

We evaluated the clinical outcomes and relapse patterns of 80 patients with primary sinonasal tract diffuse large B-cell lymphoma (SN-DLBCL) treated with rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy at 22 institutions. A total of 59 (73.8%) patients received R-CHOP chemotherapy alone, whereas 21 (26.3%) were treated with R-CHOP followed by involved field radiotherapy (IFRT). In 73 patients with Ann Arbor stage I-II disease, no significant difference was found in the response rate or overall survival (OS) between R-CHOP alone (n = 52) and R-CHOP followed by IFRT (n = 21). Among 11 relapsed patients in this study, the most common pattern of relapse was local (n = 8, 11.8%), whereas central nervous system (CNS) relapse was observed in only one (1.9%) patient. These results suggest that patients with primary SN-DLBCL treated with R-CHOP have a relatively low CNS relapse rate and better OS compared to previous studies before the introduction of R.

Role of high-dose melphalan with autologous stem cell transplantation in multiple myeloma patients receiving botezomib-containing induction therapy.

To examine the role of high-dose melphalan therapy with autologous stem cell transplantation (HDM/ASCT) in the final outcomes of multiple myeloma (MM) patients receiving bortezomib-containing induction therapy (IT), we analyzed relationships between quality of response after IT including bortezomib or HDM/ASCT and survival. In total, 92 MM patients who received IT with bortezomib followed by HDM/ASCT were enrolled. The median follow-up was 28.0 months. Three-year progression-free survival (PFS) and overall survival (OS) were 41.1 and 72.0 %, respectively. A complete response (CR) after HDM/ASCT was a strong prognostic factor for PFS and OS (p = 0.002 and 0.001, respectively). Additionally, out of 67 patients who failed to achieve CR after IT, 36 (53.7 %) patients achieved CR after HDM/ASCT. PFS and OS in patients with CR after additional HDM/ASCT were similar to those in patients who had already achieved CR after IT. However, achievement of at least very good partial response following IT with bortezomib failed to improve PFS and OS (p = 0.35 and 0.11, respectively). Thus, we conclude that post-HDM/ASCT CR is the best prognostic factor for both PFS and OS regardless of response to bortezomib. Therefore, HDM/ASCT remains an important therapy in MM patients even after introduction of bortezomib IT.

Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer's disease.

Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aß)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aß25-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.

Gastrodia elata Blume and its pure compounds protect BV-2 microglial-derived cell lines against ß-amyloid: the involvement of GRP78 and CHOP.

OBJECTIVES: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known for its therapeutic benefits against neurodegenerative diseases. Microglial activation and death have been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease. In this study, GE and its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied to ß-amyloid-induced BV2 mouse microglial cells. MATERIALS AND METHODS: Cell viability was assessed by the MTT assay and Western blotting was also performed. RESULTS: ß-amyloid-induced cell death was shown to be induced time- and dose-dependently. To examine the cell death mechanism, we confirmed the involvement of ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress protein, was expressed at high levels but glucose-regulated protein 78 (GRP78), an anti-apoptotic ER stress protein with chaperone activity, was only slightly affected by treatment with ß-amyloid. However, pretreatment with GE and its components inhibited the expression of CHOP but increased that of GRP78 in ß-amyloid-treated cells. This study also showed that a single treatment with GE extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for enhanced protein folding machinery, suggesting a protective mechanism for GE against ß-amyloid. CONCLUSIONS: This study reveals the protective effects of GE against ß-amyloid-induced cell death, possibly through the enhancement of protein folding machinery of a representative protein, GRP78, and the regulation of CHOP in BV2 mouse microglial cells.