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Background: It can be very challenging for practitioners to talk with autistic children, especially when the conversation calls for self-regulation. Self-regulation is inextricably linked to awareness of oneself and others in social contexts. Encouraging the need for autonomy could help increase self-awareness and awareness of others in social events, which in turn could strengthen self-regulation. However, little is known about how autonomy influences competence in reasoning about self and others when regarding social events in which autistic children participate. This study explores the reasoning of self-other awareness on a microlevel timescale using ipsative, dynamic approaches to autism. The central question in this study is: to what extent can autonomy-provided scaffolding (APS) elicit high levels of reasoning about self-others in social events (RSS) over time? Method: We used video-taped interaction data from three sessions between one autistic child and a practitioner, contextualized by a set of animated DSM-5-based items of social events on which the child was asked to reflect. Interaction variables were the child's level of RSS and the practitioner's level of APS. We coded the real-time interaction. Results: First, when exploring the dynamics of the microdata, we found contingency over time within sessions. Second, over the sessions, the practitioner showed a stable high level of APS, whereas the child's level of RSS increased. Third, a coupling effect between the level of APS and RSS was found within and over sessions. Salient is that the child and practitioner increasingly adapted to each other over the three sessions, and over time, high-level APS of the practitioner elicited higher levels of RSS of the child. Discussion: Because the child showed a significant improvement in RSS over time, our research question provides a promising perspective. Contrary to what one might expect in autism, APS supported the performance of the child in reasoning about self-others in social situations. These outcomes underline the importance of giving voice to autistic children. The results may encourage researchers to develop strategies and tools that can help give a voice to children, to gain more insight into the child's reasoning. This may further develop self-other awareness and self-regulation in the social events of autistic children. [ABSTRACT FROM AUTHOR]

A group of youth with severe and enduring mental health problems (SEMHP) falls between the cracks of the child-and-adolescent psychiatry (CAP) system. An insufficient understanding of these youth's mental health problems results in a failure to accurately identify and provide support to these youth. To gain a deeper understanding, the aim of this study is to explore characteristics of youth with SEMHP in clinical practice based on the experiences of youth and clinicians in CAP. This qualitative study consisted of 20 semi-structured interviews with 10 youth with lived experience and 10 specialized clinicians in CAP. Both a thematic and content analysis was conducted to identify, assess, and report themes associated with youth with SEMHP. Themes were individual characteristics such as trauma, masking, self-destructive behavior, interpersonal distrust as well as environmental and systematic characteristics including parental stressors, social isolation and societal stressors, which go beyond the existing classifications. These characteristics profoundly impact youth's daily functioning across various life domains, creating an interactive process, ultimately leading to elusive mental health problems and overwhelming feelings of hopelessness. The authors recommend proper assessment of characteristics in all life domains affected and their perpetuating effect on SEMHP during diagnostics in CAP. Engaging in a dialogue with youth themselves is crucial due to the nature of youth's characteristics, which frequently transcend traditional classifications and may not be immediately discernible. It also requires an integrated care approach, entailing collaborations between educational institutions and mental healthcare providers, and attention to potential indicators of deficits in the healthcare system and society. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a highly precise, non-invasive, and image-guided form of hypofractionated radiotherapy aimed at well-defined small targets. It is characterized by superior conformity of dose distribution, steep dose drop-off gradients, and short overall treatment time, which allow effective protection of surrounding normal tissue from high radiation doses, potentially resulting in lower toxicity and a more potent biological effect. Currently, SBRT is an established curative therapy for certain cancers and some benign tumors, as well as a valuable palliative option. There is limited experience with SBRT for de novo mucosal carcinoma of the head and neck. A systematic review of the literature and subsequent analysis of 124 patients from five studies treated between 2012 and 2020 confirmed that SBRT is an effective and relatively safe treatment for small tumor targets in de novo mucosal carcinoma of the head and neck. Standardization of SBRT practice and well-designed prospective clinical trials are highly needed. Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60–83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0–8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting. [ABSTRACT FROM AUTHOR]

Life balance is a new and important concept in occupational therapy. New measurements are needed to assess and evaluate life balance and interventions aimed to achieve this concept. This article describes the test-retest reliability of three life balance measures: the Activity Calculator (AC), Activity Card Sort (ACS-NL(18-64)) and Occupational Balance Questionnaire (OBQ11-NL). Data collection took place among 50 participants with neuromuscular diseases: facioscapulohumeral dystrophy (FSHD, n = 25) or mitochondrial myopathy (MM, n = 25). The AC, the ACS-NL(18–64) and the OBQ11-NL were assessed twice with an interval of one week. Intraclass correlation coefficients (ICC-agreement) were applied to examine test-retest reliability. The ICC of the AC-average total day score was.95 (95% CI.91-.97), whereas the ICC of the weights allocated to each activity was 0.80 (95% CI.77–0.82). The ICC of the ACS-NL(18–64) percentage retained activities was 0.92 (95% CI 0.86 − 0.96) and the ICC of the importance score per activity was-.76 (95% CI. 0.68–0.89). The ICC of the OBQ11-NL total score was.76 (95% CI 0.62–0.86). All three tools showed good to excellent test-retest reliability in a sample of patients with FSHD or MM, which is promising for its use in clinical practice and research. The AC, ACS-NL(18–64) and the OBQ11-NL are promising, reliable measures of life balance in patients with neuromuscular diseases. The development of three new instruments for life balance enlarges the possibility for health professionals to measure life balance in clinical practice and research. [ABSTRACT FROM AUTHOR]

A small group of youth and emerging adults deals with severe and enduring mental health problems (SEMHP). Current mental health care struggles to recognize and treat this group timely and adequately, leaving these youth between the cracks of the system. A first step to improve care for this group is to gain a deeper understanding of the characteristics of youth with SEMHP. Therefore, this study aimed at reviewing current literature about this target group and what is known so far about their characteristics. We included 39 studies with a focus on youth aged 12–25 years with SEMHP. After critical appraisal, a content analysis and in-depth thematic analysis were conducted. According to the included studies, youth with SEMHP were characterized by severe distress and recurrent comorbid mental health problems, with pervasive suicidality. Further, underlying trauma, family conflicts, peer rejection, deep feelings of hopelessness, and psychosocial malfunctioning characterized SEMHP. It was described that for youth with SEMHP a pervasive pattern of dysfunction in multiple domains is present leading to a detrimental impact. Subsequently, this pattern exerts a reciprocal influence on the mental health problems, causing a vicious circle further worsening SEMHP. Our findings emphasize the need for a holistic approach and to look beyond the traditional classification system in order to meet the needs of these youth with wide-ranging comorbid mental health problems. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic disrupted many areas of life, including culturally accepted practices at end-of-life care, funeral rites, and access to social, community, and professional support. This survey investigated the mental health outcomes of Australians bereaved during this time to determine how these factors might have impacted bereavement outcomes. Methods: An online survey indexing pandemic and bereavement experiences, levels of grief, depression, anxiety, and health, work, and social impairment. Latent class analysis (LCA) was used to identify groups of individuals who shared similar symptom patterns. Multinomial regressions identified pandemic-related, loss-related, and sociodemographic correlates of class membership. Results: 1911 Australian adults completed the survey. The LCA identified four classes: low symptoms (46.8%), grief (17.3%), depression/anxiety (17.7%), and grief/depression/anxiety (18.2%). The latter group reported the highest levels of health, work, and social impairment. The death of a child or partner and an inability to care for the deceased due to COVID-19 public health measures were correlated with grief symptoms (with or without depression and anxiety). Preparedness for the person's death and levels of pandemic-related loneliness and social isolation differentiated all four classes. Unemployment was associated with depression/anxiety (with or without grief). Conclusions: COVID-19 had profound impacts for the way we lived and died, with effects that are likely to ricochet through society into the foreseeable future. These lessons learned must inform policymakers and healthcare professionals to improve bereavement care and ensure preparedness during and following future predicted pandemics to prevent negative impacts. [ABSTRACT FROM AUTHOR]

In this cohort study conducted in Hong Kong where both bivalent and monovalent formulations of BNT162b2 were available, there were no significant differences in the mortality or hospitalization between those who received bivalent and monovalent mRNA as second boosters. Bivalent and monovalent mRNA boosters appear equally protective against clinical outcomes. [ABSTRACT FROM AUTHOR]

Children and adolescents are among the most vulnerable to developing posttraumatic stress in the aftermath of a disaster. This study investigated posttraumatic stress among students attending surrounding primary and secondary schools following the 2014 Hazelwood mine fire in the Latrobe Valley region of Australia. Posttraumatic stress levels of students (n = 323) attending smoke-exposed schools (n = 20) were assessed 16–21 months after the event using the Children's Revised Impact of Events Scale (CRIES). The mean CRIES total score of students attending these schools was 17.22, suggesting an overall moderate level of posttraumatic stress associated with the mine fire. Across the sample, 22% of the students (n = 23) had a CRIES score of ≥30, indicative of posttraumatic stress at a level warranting clinical concern. Students attending schools located closer to the mine (Morwell Schools) experienced significantly greater levels of posttraumatic stress (CRIES M = 21.63) compared with students attending schools located further away (Non-Morwell Schools; CRIES M = 14.70). This difference appeared to have been primarily driven by higher scoring among Morwell students on the Arousal symptom domain of the CRIES. The mean CRIES score of primary school students (M = 23.18) was over double that of secondary school students (M = 10.30) regardless of the proximity of their school to the smoke event; however, this difference did not reach statistical significance. These findings highlight the need for public health responses following disasters that include targeted mental health support for child and adolescent age-groups. [ABSTRACT FROM AUTHOR]

Background: The existing evidence base indicates increased interest in knowledge translation (KT), or, the dissemination of research to ensure uptake and impact. Given this definition, this study aimed to review existing scholarship on knowledge translation (KT) of health research to people living with disabilities (PLWD), and assess the current state of accessibility of health knowledge for people living with disabilities. Methods: Given existing heterogeneity in literature as well as a number of varying definitions for both disability and knowledge translation, a reflexive, three-phase approach was utilized to improve methodological soundness. Phase I recognizes that existing review-style studies have been conducted on disability-KT. An existing systematic review on KT specific to the field of rehabilitation and physical medicine was analyzed to assess potential best practices towards inclusivity and accessibility for people living with disability. Phase II used the Center on Knowledge Translation for Disability and Rehabilitation Research (KTDRR) database as an information-source with high-specificity to disability-health KT. Phase III sought to rapidly assess the current landscape of systematic reviews relevant to disability-health KT, with four systematic reviews meeting the inclusion criteria across Cochrane, Psycinfo, CINAHL, PubMed, Web of Science, and EMBASE. Results: The current landscape of disability-health KT is primarily targeted at health professionals who serve PLWD. PLWD are included in KT, mostly as key informants, or as study participants in KT-studies designed as health interventions. Multiple systematic reviews on disability-health KT exist, presenting vastly different foci which prevent assessment of best practices. Conclusions: KT efforts are abundant and can be seen across health research related to disabilities, generating considerable literature and systematic reviews. With regards to meeting the public health objective of equalizing and enhancing access to health knowledge, future knowledge translation efforts intending to provide PLWD with up-to-date health research can be of significant value. Key messages: - Knowledge translation emerges as the most prominently used terminology to describe research dissemination; yet, its use in a search strategy often identifies studies in which people living with disabilities as sources of knowledge as opposed to recipients of knowledge - Intentional strategies to provide equitable access to health information for people living with disabilities can be multi-phase and highly complex if the study is not structured as a health intervention - The existing landscape of systematic review on disability-KT may emphasize evaluation of the effectiveness of KT; future studies on best practices for equitable access to health research can be of significant value [ABSTRACT FROM AUTHOR]

Purpose: Literature on apraxia of speech (AOS) in Chinese speakers is sparse compared to the English literature. This study aims to examine the pitch variation skills of Cantonese adults with AOS poststroke in terms of perceptual tone accuracy, acoustic fundamental frequency (fo) changes, and repetition durations on items with different syllable structures, lexical status, and tone syllables in various positions in a sequencing context. Method: Six Cantonese adults with AOS poststroke (AOS group), six adults without AOS poststroke (nAOS group), and six healthy controls (HC group) performed the tone sequencing task (TST), which was adapted from oral diadochokinetic tasks, with three different tone syllables. Tone accuracy, fo values across 10 time points, and acoustic repetition durations were compared within and between the groups. Results: The AOS group produced significantly lower tone accuracy and different fo changes on the three Cantonese tone syllables compared with the control groups and significantly longer repetition durations than the HC group. The AOS group showed more difficulty with the tone syllables with the consonant– vowel structure, while a priming effect was observed on the T2 (high-rising) syllables with lexical meanings. A unique lowering of fo in the final syllable of the trisyllabic items was observed only in the AOS group. Conclusions: The AOS group showed degraded pitch variation skills. The effects of the three linguistic elements were discussed. Future investigations are called for to adapt the TST in other tonal languages to determine if degraded pitch variation skills are present in other tonal language speakers with AOS. [ABSTRACT FROM AUTHOR]

Infidelity is reported at high rates despite strong societal prohibitions against it, leading to questions about whether outcomes support the motives driving infidelity. Little is known about whether motives behind infidelity correspond to perceived outcomes, including regret, but such information might help to explain the paradox of the high rates. Participants were recruited from a large prospective study on monogamy. Analyses were conducted on surveys from the 94 individuals who engaged in infidelity over the year. Using structured and open-ended measures, the authors examined how infidelity evolved, patterns among motives and outcomes, and regret. Infidelity typically began at work or online, lasted about one year, and involved sex as well as feelings of infatuation or love. Most (63.4%) reported not regretting their infidelity. Motives (anger, neglect, dissatisfaction, sex) were compared with outcomes (fulfilled needs, sexual satisfaction, distress) to assess concordance. Being motivated by feelings of neglect or relationship dissatisfaction was associated with needs fulfilled by infidelity; sex as a motive was associated with sexual satisfaction as an outcome. However, concordance in motives and outcomes was unrelated to regret. [ABSTRACT FROM AUTHOR]

Objective: Worsening student mental health, along with more complex mental illness presentation and increased access to campus mental health services, has led to a mental health “crisis” on campuses. One way to address student mental health needs may be through mental health programs which have been found to increase resiliency and help-seeking, and reduce stigma. Participants: The effectiveness of The Inquiring Mind (TIM), a mental health promotion and mental illness stigma reduction program, was examined in 810 students from 16 Canadian post-secondary institutions. Methods and Results: Using a meta-analytic approach, TIM improved resiliency and decreased stigmatizing attitudes from pre to post, with medium effect sizes (d>.50). Analyses with those that completed the follow-up (about one-third of the sample) showed that effects were mostly retained at three months. Other outcomes also point to the program’s effectiveness. Conclusion: TIM appears to be an effective program for post-secondary students. However, additional research, including randomized control trials, is needed to address study limitations. [ABSTRACT FROM AUTHOR]

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty often co-occur with head-and-neck cancer (HNC) and may affect treatment outcomes, but the presence, severity, and consequences of these phenomena vary from patient to patient. It is a challenge to predict which patients have a higher risk of these phenomena, and early identification using a 'quick and easy' multi-domain screening may allow us to obtain a more holistic view of the patient's risk profile, enabling the prevention of complications and prehabilitation before the start of cancer treatment. The aim of our study was to identify the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty and their co-occurrence in all newly diagnosed HNC patients. More than three quarters of the 128 patients were at risk for OD, malnutrition, sarcopenia, and/or frailty. The advanced cancer stage was related to an increased risk of OD and higher levels of distress. Background: Head-and-neck cancer (HNC) can give rise to oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty. Early identification of these phenomena in newly diagnosed HNC patients is important to reduce the risk of complications and to improve treatment outcomes. The aim of this study was (1) to determine the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty; and (2) to investigate the relation between these phenomena and patients' age, performance status, and cancer group staging. Methods: Patients (N = 128) underwent multi-domain screening consisting of the Eating Assessment Tool-10 for OD, Short Nutritional Assessment Questionnaire and BMI for malnutrition, Short Physical Performance Battery and Hand Grip Strength for sarcopenia, and Distress Thermometer and Maastricht Frailty Screening Tool for frailty. Results: 26.2%, 31.0%, 73.0%, and 46.4% of the patients were at risk for OD, malnutrition, sarcopenia, or frailty, respectively. Patients with an advanced cancer stage had a significantly higher risk of OD and high levels of distress prior to cancer treatment. Conclusions: This study identified the risk profile of newly diagnosed HNC patients using a standardized 'quick and easy' multi-domain screening prior to cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Genome-wide DNA methylation profiling has emerged as an important diagnostic tool that complements histopathology for characterizing central nervous system (CNS) tumors. The literature describing its application in Asian countries is limited. We report the feasibility and utility of adopting such profiling for children with diagnosed CNS tumors in Hong Kong. The study included samples of 97 patients with CNS embryonal or high-grade neuroepithelial tumors (HGNETs). In our DNA methylation-profiled cohort, 67% of results correlated with the diagnosis and assigned molecular subgroup and 12% of results led to revision/reassignment of diagnosis. Patient outcomes correlated significantly with methylation-based subgroups. In addition, novel clinical–histologic–molecular associations were described. Taken together, epigenomic profiling enabled clinically relevant refinement of disease classification of pediatric CNS tumors. The availability of such methodology in Asia sets the stage for international collaborations in molecularly driven trials. This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research. [ABSTRACT FROM AUTHOR]

In daily life, failure to perceive emotional expressions can result in maladjusted behaviour. For cochlear implant users, perceiving emotional cues in sounds remains challenging, and the factors explaining the variability in patients' sensitivity to emotions are currently poorly understood. Understanding how these factors relate to auditory proficiency is a major challenge of cochlear implant research and is critical in addressing patients' limitations. To fill this gap, we evaluated different auditory perception aspects in implant users (pitch discrimination, music processing and speech intelligibility) and correlated them to their performance in an emotion recognition task. Eighty-four adults (18–76 years old) participated in our investigation; 42 cochlear implant users and 42 controls. Cochlear implant users performed worse than their controls on all tasks, and emotion perception abilities were correlated to their age and their clinical outcome as measured in the speech intelligibility task. As previously observed, emotion perception abilities declined with age (here by about 2–3% in a decade). Interestingly, even when emotional stimuli were musical, CI users' skills relied more on processes underlying speech intelligibility. These results suggest that speech processing remains a clinical priority even when one is interested in affective skills. [ABSTRACT FROM AUTHOR]

Immigrant and refugee populations face multiple barriers to accessing mental health services. This scoping review applies the (Levesque et al. in Int J Equity Health 12:18, 2013) Patient-Centred Access to Healthcare model in exploring the potential of increased access through virtual mental healthcare services VMHS for these populations by examining the affordability, availability/accommodation, and appropriateness and acceptability of virtual mental health interventions and assessments. A search in CINAHL, MEDLINE, PSYCINFO, EMBASE, SOCINDEX and SCOPUS following (Arksey and O'Malley in Int J Soc Res Methodol 8:19–32, 2005) guidelines found 44 papers and 41 unique interventions/assessment tools. Accessibility depended on individual (e.g., literacy), program (e.g., computer required) and contextual/social factors (e.g., housing characteristics, internet bandwidth). Participation often required financial and technical support, raising important questions about the generalizability and sustainability of VMHS' accessibility for immigrant and refugee populations. Given limitations in current research (i.e., frequent exclusion of patients with severe mental health issues; limited examination of cultural dimensions; de facto exclusion of those without access to technology), further research appears warranted. [ABSTRACT FROM AUTHOR]

Background: Subthreshold depression is a highly prevalent mood disorder in young adults. Mind–body exercises, such as Tai Chi, have been adopted as interventions for clinical depressive symptoms. However, the possible effect and underlying mechanism of Tai Chi on subthreshold depression of young individuals remain unclear. This randomized controlled study aimed to evaluate the effects of Tai Chi training and tested the combined stress and reward circuitry model for subthreshold depression. Results: A total of 103 participants completed this trial, with 49 in the 12-week 24-style Tai Chi group and 54 participants in control group. Our results showed significantly lower scores on depressive symptoms (P = 0.002) and anxiety symptoms (P = 0.009) and higher scores on quality of life (P = 0.002) after Tai Chi training. There were significant reductions in salivary cortisol levels (P = 0.007) and putamen gray matter volume (P < 0.001) in the Tai Chi group. The changes in cortisol levels and putamen gray matter volume had direct (bootstrapping confidence interval [− 0.91, − 0.11]) and indirect effects (bootstrapping confidence interval [− 0.65, − 0.19]) on the changes induced by Tai Chi training on depressive symptoms, respectively. Conclusion: The stress–reward complex results indicated an interaction between lowering stress levels and increasing reward circuitry activity associated with the alleviation of depressive symptoms among participants. The 12-week Tai Chi training was effective in improving the symptoms and quality of life of young adults with subthreshold depression. Trial Registration Chinese Registry of Clinical Trials (Registration Number: ChiCTR1900028289, Registered December 12, 2019). Key points: Tai Chi training improves depressive and anxiety symptoms and quality of life in young people with subthreshold depression. Improvements in depressive symptoms are associated with reduction in putamen volume and salivary cortisol levels. Involvement of the stress and reward circuit suggests Tai Chi would improve stress regulation and reward preference. [ABSTRACT FROM AUTHOR]

Aims Hypertensive heart disease (HHD) is recognized as a key clinical precursor to heart failure with preserved ejection fraction (HFPEF). However, pathophysiological transition from HHD to HFPEF is not well understood. We sought determine whether regional differences in impaired myocardial function may underlie the greater mechanical dysfunction seen in HFPEF compared to HHD. Methods and results We used standardized echocardiography to assess regional myocardial deformation in a cohort of n = 327 adults with preserved left ventricular (LV) ejection fraction (≥45%), including: n = 129 with HFPEF, n = 158 with HHD and no heart failure, and n = 40 normotensive controls. From detailed measurements of LV systolic strain performed in multiple views, we derived and then compared regional measures of basal, mid-ventricular, and apical longitudinal strains. In models adjusting for clinical covariates, basal and mid-ventricular LV myocardial deformation was more impaired in HHD than in controls (P ≤ 0.003), whereas apical deformation was more impaired in HFPEF than in HHD (P = 0.005). In multivariable-adjusted analyses, only apical strain remained independently associated with HFPEF vs. HHD status [odds ratio 1.18 (1.02–1.37), P = 0.030 per 1% decrease in apical strain]. Compared to other regional strains, apical longitudinal strain optimally differentiated HFPEF from HHD (area under the receiver operating curve: apical longitudinal strain = 0.67; mid-ventricular longitudinal strain = 0.59; basal longitudinal strain = 0.60). Conclusion We found that while apical mechanical function is preserved in HHD, it was impaired in HFPEF and may contribute to the transition from an asymptomatic heart disease to a symptomatic heart disease. [ABSTRACT FROM AUTHOR]

Research on dementia literacy in Chinese societies is still emerging, and this is especially the case among racially minoritized groups. The present study explored the knowledge, causal beliefs, and help-seeking behaviors of South Asian migrants in Hong Kong about dementia. It also investigated existing community barriers related to dementia knowledge and help-seeking. We conducted a qualitative study from a purposive sample of 38 older people and family caregivers from India, Pakistan, and Nepal who lived in Hong Kong. Focus groups and individual in-depth interviews were used to gather information, while thematic analysis was employed to analyze the data. Five main themes were identified: normalization with stigmatization of dementia; spiritual and psychosocial attributions of dementia; familial responsibility despite potential caregiving burden; uncertainties versus openness to professional care; and barriers and opportunities in dementia literacy. Ethnic minorities recognized dementia as a disease of normal aging or a mental disorder. They also perceived spiritual and psychosocial factors as their main causes. While participants recognized the potential burden of dementia caregiving, families were their first point of help-seeking, as many of them expressed contrasting feelings of confidence or doubt toward professional services. Utilization of health education strategies, together with collaboration with community leaders, could address the barriers to dementia literacy. This is the first study to explore how ethnic minorities in Asia perceive dementia and its related help-seeking behaviors in their communities. South Asian migrants in Hong Kong have a limited understanding of dementia and may experience delays in obtaining relevant community services. While culture influenced their knowledge, health education may address their misperceptions and help-seeking behaviors toward dementia. Culture- and language-specific programs could also improve dementia knowledge and health service access. [ABSTRACT FROM AUTHOR]

Nightshift work disturbs the circadian rhythm, which might contribute to the development of cardio-metabolic disorders. In this cross-sectional study, we aimed to gain insight into perturbations of disease relevant metabolic pathways due to nightshift work. We characterized the metabolic profiles of 237 female nurses and paramedic staff participating in the Klokwerk study using the Nightingale Health platform. We performed analyses on plasma levels of 225 metabolites, including cholesterol, triglycerides, fatty acids, and amino acids. Using both principal component- and univariate-regression, we compared metabolic profiles of nightshift workers to metabolic profiles from workers that did not work night shifts (defined as day workers). We also assessed whether differential effects were observed between recently started versus more experienced workers. Within the group of nightshift workers, we compared metabolic profiles measured right after a nightshift with metabolic profiles measured on a day when no nightshift work was conducted. We observed evidence for an impact of nightshift work on the presence of unfavorable fatty acid profiles in blood. Amongst the fatty acids, effects were most prominent for PUFA/FA ratios (consistently decreased) and SFA/FA ratios (consistently elevated). This pattern of less favorable fatty acid profiles was also observed in samples collected directly after a night shift. Amino acid levels (histidine, glutamine, isoleucine, and leucine) and lipoproteins (especially HDL-cholesterol, VLDL-cholesterol, and triglycerides) were elevated when comparing nightshift workers with day workers. Amino acid levels were decreased in the samples that were collected directly after working a nightshift (compared to levels in samples that were collected during a non-nightshift period). The observed effects were generally more pronounced in samples collected directly after the nightshift and among recently started compared to more experienced nightshift workers. Our finding of a suggested impact of shift work on impaired lipid metabolism is in line with evidence that links disruption of circadian rhythmicity to obesity and metabolic disorders. [ABSTRACT FROM AUTHOR]

Lesbian and gay adults' self-reported experiences of violence from family of origin in adulthood have been less examined in previous research on interpersonal violence from intimate others. In China, while it has been understood that lesbians and gay men face mounting pressure to marry and have children, there is little empirical evidence on their experiences of violence from family of origin. This paper analyzes self-reported experiences of negative treatment and violence from a larger-scale study in China of 11,048 Chinese lesbian and gay cisgender adults. The majority of Chinese lesbians and gay men felt pressure to get married and have children (70.4%), and experienced different forms of negative treatment and violence from their family members based on sexual orientation (54.2%). A significant gender difference was observed. This paper provides novel empirical evidence for the lived experiences of lesbians and gay men in China and bears implications for China's Anti-domestic Violence Law. [ABSTRACT FROM AUTHOR]

Objectives: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines. Design: A prospective population-based cohort study. Setting and Participants: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022. Measurements: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria. Results: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04–2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality. Conclusion: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk. [ABSTRACT FROM AUTHOR]

Childhood apraxia of speech (CAS) is a paediatric motor speech disorder. We investigated the lexical tone perception and production abilities of children with CAS and the relationships between the two. Three children with CAS, aged between 3;7 and 5;8, were given the Cantonese Tone Identification Test (CANTIT) and the Hong Kong Cantonese Articulation Test (HKCAT) for assessment of tone perception and production, respectively. Accuracy and error patterns were investigated based on their performance on the two tests. Correlation analysis was performed on children's perception and production scores. Two children scored at the lowest rank on the CANTIT, while one child obtained a Z score of 0. All children scored three standard deviations below the mean on the HKCAT. No statistical differences were found among the six tones with respect to perception accuracy, H(5) = 3.731, p = 0.589. Error analysis showed that children with CAS demonstrated more confusion on perceiving tones compared with TD peers. There were no main effects for task (F(1,2) = 0.040, p = 0.859) or tone (F(5,10 = 0.997, p = 0.467); nor were there task or tone interaction effects on perception versus production accuracy (F(5,10) = 1.772, p = 0.206). Tone perception and production accuracy were not significantly correlated (r2 = 0.181, p = 0.078). Tone perception deficits were evident in two out of three children with CAS, while all children had lexical tone production difficulties. In this small sample, tone production was more universally affected than tone perception. [ABSTRACT FROM AUTHOR]

A projected rise in patients with complex health needs and a rapidly ageing population will place an increased burden on the healthcare system. Care coordination can bridge potential gaps during care transitions and across the care continuum to facilitate care integration and the delivery of personalised care. Despite having a national strategic vision of improving care integration across different levels of care and community partners, there is no consolidation of evidence specifically on the salient dimensions of care coordination in the Singapore healthcare context. Hence, this scoping review aims to uncover the key themes that facilitate care coordination for patients with chronic conditions in Singapore to be managed in the community while illuminating under-researched areas in care coordination requiring further exploration. The databases searched were PubMed, CINAHL, Scopus, Embase, and Cochrane Library. Results from Google Scholar were also included. Two independent reviewers screened articles in a two-stage screening process based on the Cochrane scoping review guidelines. Recommendation for inclusion was indicated on a three-point scale and rating conflicts were resolved through discussion. Of the 5792 articles identified, 28 were included in the final review. Key cross-cutting themes such as having standards and guidelines for care programmes, forging stronger partnerships across providers, an interoperable information system across care interfaces, strong programme leadership, financial and technical resource availabilities and patient and provider-specific factors emerged. This review also recommends leveraging these themes to align with Singapore's national healthcare vision to contain rising healthcare costs. [ABSTRACT FROM AUTHOR]

Previous studies have primarily used an individual differences approach to identify dispositional factors associated with bullying behavior, which often neglect the broader school context in which bullying occurs. The present study used a multilevel research design to examine the contextual influence of school normative climate on allyship, bullying, and internalized homonegativity. The study included 3020 students (M = 15.83 years, SD = 1.50) from ten secondary schools in China. The results showed that school-level gender role attitudes were positively associated with bullying perpetration among heterosexual students as well as bullying victimization and internalized homonegativity among LGBQA+ students. In addition, there was a negative association between school-level sexual prejudice and allyship among heterosexual students. The findings demonstrate the contextual influence of school normative climate and highlight the need for regular school climate assessments, so that appropriate instructions, policies, and practices can be implemented to address gender biases and homophobia and the resulting bullying behavior. [ABSTRACT FROM AUTHOR]

This study aimed to identify and assess the evidence on the association between idiopathic chronic low back pain (LBP) and cognitive function in individuals with LBP. A secondary aim was to explore whether changes in cognitive function are associated with pain characteristics and psychological factors (eg, catastrophizing and fear of movement). Eleven studies were included in this systematic review, and four meta‐analyses were conducted. Low to very low‐quality evidence suggests impaired cognitive function in individuals with LBP compared to asymptomatic controls for problem solving (k = 5; d = 0.33; CI = 0.16–0.50; z = 3.85 p = 0.0001), speed of information processing (k = 5; d = 0.44; CI = 0.22–0.65; z = 4.02 p < 0.0001), working memory (k = 6; d = 0.50; CI = 0.34–0.66; z = 6.09 p < 0.0001), and delayed memory (k = 3; d = 0.34; CI = 0.07–0.6, z = 2.49 p = 0.02). The association between LBP intensity and psychological factors and cognitive function was inconclusive. More studies are needed to explore these associations and improve evidence in this field. The results of this study suggest that cognitive aspects should be considered during the rehabilitation process of patients with LBP and raise further questions, including whether individuals with LBP are at a greater risk of developing dementia or whether targeting cognitive function will increase the probability of success of LBP treatment. These questions should, also, be considered in future studies. [ABSTRACT FROM AUTHOR]

Exoskeleton use by people with complete spinal cord injury (SCI) in daily life is challenging. To optimize daily exoskeleton use, a better understanding of the purpose of use and the accompanying improvements are needed. The perspective of experienced exoskeleton users could guide design improvements. Face-to-face semi-structured interviews were held with 13 people with SCI with exoskeleton experience. Interviews were audio-taped, transcribed, and analysed thematically. Participants expressed three future purposes of exoskeleton use: for daily activities (e.g., stair climbing), exercise (e.g., staying healthy), and social interaction (e.g., standing at parties). Exoskeleton use during daily activities was the ultimate goal. Therefore, the future exoskeleton should be: easy to use, small and lightweight, tailor made, safe, comfortable, less distinctive, durable, and affordable. Improving the ease of use was relevant for all purposes, for all participants. The other suggestions for improvement varied depending on the purpose of use and the participant. Increasingly more advanced improvements are needed to transition from an exercise purpose to social interaction, and ultimately use during daily activities. In the current study, detailed suggestions for improvements have been made. Only when multiple of these suggestions are adjusted, can the exoskeleton be used to its full potential. The use of an exoskeleton by people with a complete spinal cord injury in daily life is still in its infancy. To optimize daily exoskeleton use, a better understanding of the purpose of use and exoskeleton improvements is needed. More advanced improvements to future exoskeletons are needed to make a transition from use as an exercise device to use during social interaction and daily activities. Improving the ease of use of future exoskeletons is considered a priority by experienced users, followed by making the exoskeleton small, lightweight, and tailor made. [ABSTRACT FROM AUTHOR]

Knee pain has an incidence of approximately 25% in adults and its prevalence has been increasing in the last 20 years. The use of smartphones and mobile applications (apps) has also increased in the 'Health and Fitness' field, which might be a useful complement in the rehabilitation process of these patients. However, it is necessary to investigate the quality of these mobile applications. Aim: This study aimed to assess free mobile apps targeting knee pain and to characterise and critically analyse the interventions described in them. Methods: A systematic search was performed in the Apple store, Play Store and Microsoft Store. Results: A total of 26 applications met the inclusion criteria and were evaluated using the Mobile Apps Rating Scale (MARS), and for their content against guidelines on knee pain intervention. The mean MARS total score was 3.3 (±0.5) and the mean subjective quality score was 2.1 (±0.9) out of a maximum of 5 points each. Most apps combined different types of exercises 88% and included both exercise and pain education (62%). Results: These results suggest a need to improve the quality of these apps aiming to create more engagement and improve app usage. Additionally, as health apps may be useful in pain management and be an alternative to complement rehabilitation, the involvement of health professionals is important during the development process of the apps including evidence‐based content and progression recommendations. [ABSTRACT FROM AUTHOR]

Purpose: Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. Methods: We examined cross-sectional subsets from the CODAM cohort (n = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC–MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. Results: Methionine was associated with all measures of liver fat, e.g., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: β = 0.19 (0.09, 0.28); DMS: β = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: β = 0.15 (0.08, 0.23); DMS: β = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: β = 0.16 (0.08, 0.25); DMS: β = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. Conclusion: Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence of benign paroxysmal positional vertigo subtype by hospital visit type (i.e. out-patient department vs emergency room), in a single tertiary referral centre. Methods: A total of 772 consecutive patients with benign paroxysmal positional vertigo were included. Using head-roll and Dix–Hallpike tests, benign paroxysmal positional vertigo subtype was determined as canalolithiasis posterior semicircular canal benign paroxysmal positional vertigo, geotropic horizontal semicircular canal benign paroxysmal positional vertigo or apogeotropic benign paroxysmal positional vertigo. Results: The posterior semicircular canal benign paroxysmal positional vertigo patients who were evaluated via the out-patient department outnumbered those evaluated via the emergency room, while those with horizontal semicircular canal benign paroxysmal positional vertigo who were evaluated via the emergency room outnumbered those evaluated via the out-patient department. Conclusion: A significantly higher proportion of patients who visited the emergency room had horizontal semicircular canal benign paroxysmal positional vertigo than posterior semicircular canal benign paroxysmal positional vertigo. These results suggest that the true incidence of horizontal semicircular canal benign paroxysmal positional vertigo might be higher than previously reported. [ABSTRACT FROM AUTHOR]

Graph: Figure 1. class="chapter-para">wgMLST tree of 394 carbapenemase-producing E. coli isolates showing a genetic cluster of OXA-244-producing E. coli ST38. Genetic cluster of OXA-244 carbapenemase-producing Escherichia coli ST38 with putative uropathogenicity factors in the Netherlands Seventeen of these 30 OXA-244-producing ST38 I E. coli i isolates formed a genetic cluster based on wgMLST and was termed EcoCluster-023. [Extracted from the article]

Sexual minority stress affects not only lesbian, gay, and bisexual (LGB) individuals, but also their families. Due to the pervasiveness of stigma and discrimination, parents of LGB children often express concerns about the public perception of their child's sexual orientation and its possible impact on children, parents, and families. The concerns are particularly pertinent to parents in Chinese families, where there is a strong bond between parents and children. The present study seeks to understand the different dimensions of concerns among Chinese parents of LGB children and examine how these concerns affect their mental health. A total of 146 parents of LGB children in Hong Kong were recruited to participate in a survey regarding attitudes and concerns about their child's sexual orientation. The results revealed three areas of concern, which reflect parental worries about how a child's LGB identity may negatively impact the child, parent, and family. Parents who viewed homosexuality and bisexuality as innate and accepted their child's sexual orientation were likely to show fewer concerns. The results of structural equation modeling indicated that parental acceptance was negatively related to depression and anxiety symptoms through lower levels of child-oriented and family-oriented concerns. As accepting a child's sexual orientation is the key to reducing parental concerns and mental health problems, family-focused psychoeducation is needed to provide parents with accurate information about sexual orientation and foster supportive attitudes toward their LGB child. Clinicians and human service providers should also address child-oriented and family-oriented concerns among parents of LGB adolescents who are more inclined to be concerned about their child's sexual orientation. [ABSTRACT FROM AUTHOR]

Previous estimates suggest that there are at least nine million transgender people in Asia-Pacific; however, in most countries, legal gender recognition has not been made possible or there are otherwise stringent eligibility criteria. The obligation of having undergone gender-affirming medical interventions as a basis for such recognition is being hotly debated. However, there has been little empirical evidence on the desire to undergo various gender-affirming medical interventions among transgender people. This study fills the research gap by studying Hong Kong, where a transgender person must produce medical evidence for "complete" sex reassignment surgery in order to change the sex entry on their identity card. A community-driven survey of 234 transgender people found that only 13.0% of the participants who were assigned male at birth could fit such a requirement. Strikingly, because none of the participants assigned female at birth had undergone construction of a penis or some form of a penis, all of them would be excluded from legal gender recognition. Financial reasons and reservations about surgical risks and/or techniques were the most commonly cited reasons for not undertaking the medical interventions. The findings suggest that an overwhelming majority of transgender people in Hong Kong are excluded from legal gender recognition, which fundamentally affects their civil, political, economic, social, and cultural rights. More generally, this study shows heterogeneity among transgender people in the desire for different gender-affirming medical interventions, and thus argues that the legal gender recognition debate needs to consider their concerns and self-determination. [ABSTRACT FROM AUTHOR]

Background: Early difficult temperament and child mental health problems are consistently associated with impaired functioning in adulthood. We examined three potential pathways between difficult temperament in toddlerhood (age 2) and depressive symptoms (ages 21-23) and well-being (age 23): i) direct - early difficult temperament directly associates with these outcomes, ii) mediated - these direct effects are also mediated by a general psychopathology factor in late childhood/early adolescence (GPF; ages 7, 10,and 13), and iii) moderated-mediated - these mediated effects are also moderated by negative (age 42 months) and positive (age 33 months) parenting behaviors.Methods: The analytic sample included 1892 mother-child dyads (33.4% male children) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers reported on their child's difficult temperament, negative parenting, positive parenting, and child's mental health symptoms. In adulthood, participants reported their own depressive symptoms and well-being (i.e. mental well-being, life satisfaction, happiness).Results: First, early difficult temperament associated directly and positively with depressive symptoms, but negatively with well-being in adulthood. Second, the GPF in late childhood/early adolescence mediated these direct associations. Third, the mediated pathways were not moderated by negative or positive parenting.Limitations: i) low risk community sample, ii) early risks are based on maternal reports.Conclusions: Temperament is a risk factor for impaired psychosocial functioning in adulthood, manifested through increased susceptibility to psychopathology in childhood/adolescence. Although more research is needed to test their generalizability, these findings suggest that targeting early difficult temperament may alleviate the risk for later mental health difficulties and may increase general well-being. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews (SRs) synthesise the best evidence of effectiveness and safety on Chinese herbal medicine (CHM). Decision-making should be supported by the high-quality evidence of prudently conducted SRs, but the trustworthiness of conclusions may be limited by poor methodological rigour. Methods: This survey aimed to examine the methodological quality of a representative sample of SRs on CHM published during January 2018 to March 2020. We conducted literature search in Cochrane Database of Systematic Reviews, MEDLINE via Ovid, and EMBASE via Ovid. Eligible SRs must be in Chinese or English with at least one meta-analysis on the treatment effect of any CHM documented in the 2015 Chinese Pharmacopoeia. Two reviewers extracted the bibliographical characteristics of SRs and appraised their methodological quality using AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews 2). The associations between bibliographical characteristics and methodological quality were investigated using Kruskal-Wallis tests and Spearman's rank correlation coefficients. Results: We sampled and appraised one hundred forty-eight SRs. Overall, one (0.7%) was of high methodological quality; zero (0%), four (2.7%), and one-hundred forty-three (96.6%) SRs were of moderate, low, and critically-low quality. Only thirteen SRs (8.8%) provided a pre-defined protocol; none (0%) provided justifications for including particular primary study designs; six (4.1%) conducted a comprehensive literature search; two (1.4%) provided a list of excluded studies; nine (6.1%) undertook meta-analysis with appropriate methods; and seven (4.7%) reported funding sources of included primary studies. Cochrane reviews had higher overall quality than non-Cochrane reviews (P < 0.001). SRs with European funding support were less likely to have critically-low quality when compared with their counterparts (P = 0.020). SRs conducted by more authors (rs = 0.23; P = 0.006) and published in higher impact factor journals (rs = 0.20; P = 0.044) were associated with higher methodological quality. Conclusions: Our results indicated that the methodological quality of SRs on CHM is low. Future authors should enhance the methodological quality through registering a priori protocols, justifying selection of study designs, conducting comprehensive literature search, providing a list of excluded studies with rationales, using appropriate method for meta-analyses, and reporting funding sources among primary studies. [ABSTRACT FROM AUTHOR]

Study Question: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period?Summary Answer: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution.What Is Known Already: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth.Study Design, Size, Duration: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed.Participants/materials, Setting, Methods: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK).Main Results and the Role Of Chance: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth.Limitations, Reasons For Caution: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now.Wider Implications Of the Findings: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date.Study Funding/competing Interest(s): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial.Trial Registration Number: Netherlands Trial Register (NL5193/NTR 5342). [ABSTRACT FROM AUTHOR]

Study Question: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation?Summary Answer: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years.What Is Known Already: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment.Study Design, Size, Duration: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016.Participants/materials, Setting, Methods: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs.Main Results and the Role Of Chance: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08).Limitations, Reasons For Caution: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation.Wider Implications Of the Findings: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk.Study Funding/competing Interest(s): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

This study examined the prosodic realization of recurrent multiword combinations (RMC) in Mandarin spontaneous speech production and asked (a) whether speakers produce RMCs differently compared to novel combinations, and (b) how the RMC durational patterns are connected to its distributional properties and constituent structures. RMCs were first defined based on their distributional criteria in a large representative corpus, and a subset of these RMCs used in a phone-aligned spontaneous speech corpus were identified for the analyses of the relationship between their duration on one end and their distributional statistics (RMC frequency and lexical associations in two directions) and constituent structures (projected constituent level and boundary) on the other. The results suggest that Mandarin speakers are sensitive to the multifaceted multiword distributional properties, which are mediated by the constituent structures of RMCs. We discuss how these distinct durational patterns contribute to our understanding of the pragmatic and interactional role of multiword units in language processing and development. [ABSTRACT FROM AUTHOR]

Background: Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction; however, the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis, and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined Post Operative Radiation Therapy in Endometrial Carcinoma-1, -2, and -3 trial cohort.Methods: After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into 3 groups according to the molecular cause of their MMRd-EC. Kaplan-Meier method, log-rank test, and Cox model were used for survival analysis. Competing risk analysis was used to estimate the subsequent cancer probability. All statistical tests were 2-sided.Results: Among the 1336 ECs, 410 (30.7%) were MMRd. A total of 380 (92.7%) were fully triaged: 275 (72.4%) were MLH1-hypermethylated MMRd-ECs; 36 (9.5%) LS MMRd-ECs, and 69 (18.2%) MMRd-ECs due to other causes. Limiting screening of EC patients to 60 years or younger or to 70 years or younger would have resulted in missing 18 (50.0%) and 6 (16.7%) LS diagnoses, respectively. Five-year recurrence-free survival was 91.7% (95% confidence interval [CI] = 83.1% to 100%; hazard ratio = 0.45, 95% CI = 0.16 to 1.24, P = .12) for LS, 95.5% (95% CI = 90.7% to 100%; hazard ratio = 0.17, 95% CI = 0.05 to 0.55, P = .003) for "other" vs 78.6% (95% CI = 73.8% to 83.7%) for MLH1-hypermethylated MMRd-EC. The probability of subsequent LS-associated cancer at 10 years was 11.6% (95% CI = 0.0% to 24.7%), 1.5% (95% CI = 0.0% to 4.3%), and 7.0% (95% CI = 3.0% to 10.9%) within the LS, "other," and MLH1-hypermethylated MMRd-EC groups, respectively.Conclusions: The LS prevalence in the Post Operative Radiation Therapy in Endometrial Carcinoma trial population was 2.8% and among MMRd-ECs was 9.5%. Patients with LS-associated ECs showed a trend towards better recurrence-free survival and higher risk for second cancers compared with patients with MLH1-hypermethylated MMRd-EC. [ABSTRACT FROM AUTHOR]

Study Question: Is fertility treatment with clomiphene citrate associated with an increased risk of childhood epilepsy, including specific subtypes of epilepsy?Summary Answer: Fertility treatment with clomiphene citrate may be associated with a small increased risk of idiopathic generalized epilepsy and focal epilepsy in childhood.What Is Known Already: Clomiphene citrate is among the most commonly prescribed drugs for fertility treatment. However, concerns have been raised as to whether the treatment may harm the developing fetus.Study Design, Size, Duration: This nationwide cohort study included all pregnancies in Denmark from 1 July 1995 resulting in a live-born singleton child before 31 December 2013. The children were followed until 31 December 2016.Participants/materials, Setting, Methods: Children conceived after fertility treatment with clomiphene citrate were identified from the Danish National Prescription Registry. The primary outcomes were childhood epilepsy, idiopathic generalized epilepsy, and focal epilepsy identified from the Danish National Patient Register and from antiepileptic drug prescriptions in the Danish National Prescription Registry. All analyses were conducted using Cox proportional hazards regression.Main Results and the Role Of Chance: A total of 1 081 291 pregnancies were included; 12 644 children (1.2%) developed epilepsy. Fertility treatment with clomiphene citrate was associated with a small increased risk of childhood epilepsy (hazard ratio [HR]: 1.10; 95% CI: 1.00-1.22), idiopathic generalized epilepsy (HR: 1.41; 95% CI: 1.16-1.72), and focal epilepsy (HR: 1.26; 95% CI: 1.04-1.53).Limitations, Reasons For Caution: The increased risk of idiopathic generalized epilepsy may be due to confounding from time stable parental characteristics related to treatment with clomiphene citrate, since the association was strongest with the lowest administered dosage of clomiphene citrate prior to conception, and the association disappeared in a sibling analysis.Wider Implications Of the Findings: The increased risk of focal epilepsy may be related to the hormonal treatment, since the association tended to increase with increasing cumulative dosage of clomiphene citrate prior to conception, and the association persisted in a sibling analysis. This finding may be of clinical importance, since alternative hormones are available for fertility treatment.Study Funding/competing Interest(s): Financial support from Aarhus University and the Aase and Ejnar Danielsen Foundation. U.S.K. received personal teaching fees from Merck, outside the submitted work.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy.Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation.Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome.Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support.Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025.Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002).Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation.Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448. [ABSTRACT FROM AUTHOR]

Few data are available that have compared outcomes with different EGFR tyrosine kinase inhibitors (TKIs) specifically in Asian patients with EGFR mutation-positive non-small-cell lung cancer. In this narrative review, we have collated available data from prospective studies that have assessed first-, second- and third-generation EGFR TKIs in Asian populations, including subanalyses in individual countries (China and Japan). These data indicate that outcomes with first- and second-generation TKIs are broadly similar in Asian and non-Asian populations. However, while the third-generation EGFR TKI, osimertinib, confers significant overall survival benefit over erlotinib/gefitinib in non-Asians, this is not apparent in Asians, particularly in countries like Japan with well-resourced healthcare. Head-to-head comparisons of second- and third-generation EGFR TKIs, with OS as a primary end point, should be considered in Asia. [ABSTRACT FROM AUTHOR]

Introduction: Pitch variation, which refers to one's ability to vary fundamental frequency (F0) within or between syllables when speaking, has not been investigated in children with childhood apraxia of speech (CAS). However, pitch variation plays an important role in tone languages, as varying F0 patterns communicate different lexical meanings. This study investigated pitch variation abilities in individuals with CAS via the tone-sequencing tasks (TSTs), focusing on task performance and the effects of syllable structure, lexical status, and tones. Method: Three Cantonese-speaking children with CAS (aged 3;7-5;8 [years;months]) and six children without CAS participated in the study. Children without CAS were divided into two control groups, comprising those with speech and/or language impairment or typical development. TSTs consisted of 56 sets of five repetitions of stimuli. The stimuli varied in syllable structure, lexical status, and tones. Percentage of tones correct (PTC), consistency scores, F0 values, and acoustic repetition duration were measured. Results: The CAS group performed more poorly than the control groups on the TST with respect to tone accuracy, consistency, and repetition duration. No interaction effects between group and syllable structure or group and lexical status were found. No significant difference was found on F0 values across time between Tone 1 and Tone 2 syllables in the CAS group. However, interaction effects between group and time points of F0 values on Tone 2 syllables were found. Discussion: The results suggest that children with CAS have difficulty with pitch variation, which was revealed on the TST with respect to tone accuracy, consistency, and repetition duration. Moreover, children with CAS have difficulty in varying F0 values to produce high-rising tones and tend to use high-level tones to substitute. Clinically, the TST may be useful to assist in the diagnosis of CAS. Isolated vowel stimuli may be useful to test young children or children with severe impairment. Future investigations and development of a normed tool for children with CAS are suggested. [ABSTRACT FROM AUTHOR]

Objective: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level).Methods: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155).Results: The STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008).Conclusions: Predefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support.Key Points: • In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support. [ABSTRACT FROM AUTHOR]

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans. [ABSTRACT FROM AUTHOR]

Study Question: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?Summary Answer: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.What Is Known Already: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability.Study Design, Size, Duration: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391).Participants/materials, Setting, Methods: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis.Main Results and the Role Of Chance: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00).Limitations, Reasons For Caution: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function.Wider Implications Of the Findings: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer.Study Funding/competing Interest(s): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

PURPOSE Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. METHODS We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation. RESULTS We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19). CONCLUSION Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL).Methods: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication.Results: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45).Conclusions: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products. [ABSTRACT FROM AUTHOR]

Objectives: To (a) compare palliative care needs of lung cancer patients on their final admission to community‐based and inpatient palliative care services; and (b) explore whether and how these care needs affect their utilisation of different palliative care services in the last days of life. Methods: Descriptive study involving 17,816 lung cancer patients who received the last episode of palliative care from specialist services and died between 1 January 2013 and 31 December 2018. Results: Both groups of patients admitted to community‐based and inpatient palliative care services generally experienced relatively low levels of symptom distress, but high levels of functional impairment and dependency. "Unstable" versus "stable" palliative care phase (Odds ratio = 11.66; 95% Confidence Interval: 9.55–14.24), poorer functional outcomes and severe levels of distress from many symptoms predicted greater likelihood of use of inpatient versus community‐based palliative care. Conclusions: Most inpatient palliative care admissions are not associated with high levels of symptom severity. To extend the period of home care and rate of home death for people with lung cancer, additional investment is required to improve their access to sufficiently skilled palliative care staff, multi‐disciplinary teams and 24‐hour home support in community settings. [ABSTRACT FROM AUTHOR]