Clinical prediction models in children that use repeated measurements with time-varying covariates: a scoping review.

BACKGROUND: Emerging evidence suggests that clinical prediction models that use repeated (time-varying) measurements within each patient may have higher predictive accuracy than models that use patient information from a single measurement. OBJECTIVE: To determine the breadth of the published literature reporting the development of clinical prediction models in children that use time-varying predictors. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases. ELIGIBILITY CRITERIA: We included studies reporting the development of a multivariable clinical prediction model in children, with or without validation, to predict a repeatedly measured binary or time-to-event outcome and utilizing at least one repeatedly measured predictor. SYNTHESIS METHODS: We categorized included studies by the method used to model time-varying predictors. RESULTS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27 (27%) used methods that incorporated the repeated measurements as time-varying predictors in a single model. Among these 27 time-varying prediction model studies, we grouped model types into nine categories: time-dependent Cox regression, generalized estimating equations, random effects model, landmark model, joint model, neural network, K-nearest neighbor, support vector machine and tree-based algorithms. Where there was comparison of time-varying models to single measurement models, using time-varying predictors improved predictive accuracy. CONCLUSIONS: Various methods have been used to develop time-varying prediction models in children, but there is a paucity of pediatric time-varying models in the literature. Incorporating time-varying covariates in pediatric prediction models may improve predictive accuracy. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy. WHAT THIS SCOPING REVIEW ADDS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27% used analytical methods that incorporated time-varying covariates. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy. HOW TO USE THIS SCOPING REVIEW: We summarized methods used to develop pediatric clinical prediction models that incorporate repeated measurements with time-varying covariates. Researchers may use the findings of this review to identify appropriate analytical methods for developing a time-varying prediction model in pediatric care.

Pathway analysis between dental caries and oral health-related quality of life in the transition from childhood to adolescence: a 10-year cohort study.

PURPOSE: To evaluate the direct and indirect pathways between cavitated carious lesions and oral health-related quality of life (OHRQoL) during the transition from childhood to adolescence. METHODS: A prospective cohort study followed an initial sample of 639 children (one to five years old), in southern Brazil for ten years. In addition to the baseline (T1), two subsequent reassessments were conducted after seven (T2) and ten years (T3). OHRQoL was measured through the Early Childhood Oral Health Impact Scale (ECOHIS) and Child Perceptions Questionnaire (CPQ8-10 and CPQ11-14), according to the age group. Dental caries was evaluated using the International Caries Detection and Assessment System (ICDAS) in the three waves. Socioeconomic variables and other factors related to oral health (frequency of toothbrushing and toothache) were also collected. Structural equation modeling was used to estimate the direct and indirect effects among the variables over ten years. RESULTS: A total of 449 and 429 children were reevaluated at T2 and T3 (positive response rates of 70.3% and 67.1%, respectively). Dental caries in T1 and T2 directly predicted the occurrence of a worse OHRQoL in the respective follow-up periods. Dental caries at T3 indirectly predicted a worse OHRQoL (T3), via toothache. Dental caries at T1 and T2 directly predicted the occurrence of dental caries at T3, while a worse OHRQoL at T2 directly predicted a worse OHRQoL at T3. CONCLUSION: Dental caries negatively impacts, directly and indirectly, the OHRQoL from early childhood to adolescence.

Youth adversity and trajectories of depression/anxiety symptoms in adolescence in the context of intersectionality in the United Kingdom.

BACKGROUND: Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality. METHODS: Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11-14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11-12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention. CONCLUSIONS: The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.

Examining compulsive exercise as a risk factor for eating disorder symptoms in first-year college students using a latent change score modeling approach.

OBJECTIVE: Research suggests that both compulsive exercise and eating disordered behaviors increase during college. Despite strong cross-sectional associations between compulsive exercise and eating disorders, it is unknown if compulsive exercise is a variable risk factor for eating disorders or simply a correlate. It was hypothesized that increases in compulsive exercise would significantly and prospectively predict increases in overall number of eating disorder symptoms over the study period. METHOD: A total of 265 first year college students who did not meet criteria for a full or subthreshold eating disorder diagnosis at Time 1 (age M = 18.15; SD = 0.42; 122 female [46%] at Time 1) completed reports of compulsive exercise and eating disorder symptoms via online questionnaires at four timepoints over the 9-month 2021-2022 academic year (76% retention rate). Hypotheses were tested using a bivariate latent change score model. RESULTS: Hypotheses were not supported. Change in compulsive exercise did not predict change in number of eating disorder symptoms. Change in number of eating disorder symptoms also did not predict change in compulsive exercise. CONCLUSIONS: Compulsive exercise did not emerge as a variable risk factor for the development of eating disorder symptoms among first year college students. The relationship between these behaviors should be investigated at different developmental timepoints, such as early adolescence, and potential third variables that may explain the observed co-occurrence should be explored. PUBLIC SIGNIFICANCE: This study investigated whether increases in compulsive exercise predicted increases in number of eating disorder symptoms among first year college students. Compulsive exercise did not significantly predict number of eating disorder symptoms. Additional research is warranted to clarify the relationship between compulsive exercise and eating disorder symptoms.

Changed sleep according to weighted blanket adherence in a 16-week sleep intervention among children with attention-deficit/hyperactivity disorder.

STUDY OBJECTIVES: To examine differences in sample characteristics and longitudinal sleep outcomes according to weighted blanket adherence. METHODS: Children with attention-deficit/hyperactivity disorder (ADHD) (n =94), mean age 9.0 (sd 2.2, range 6-14) participated in a 16-week sleep intervention with weighted blankets (WB). Children were classified as WB adherent (use of WB ≥ 4 nights/week) or non-adherent (use of WB ≤ 3 nights/week). Changes in objectively measured sleep by actigraphy, parent-reported sleep problems (Children's Sleep Habits Questionnaire (CSHQ)) and child-reported Insomnia Severity Index (ISI) were evaluated according to adherence with mixed effect models. Gender, age, and ADHD subtype were examined as potential moderators. RESULTS: Children adherent to WBs (48/94) showed an early response in sleep outcomes and an acceptance of the WB after four weeks of use as well as a decrease in parent- (CSHQ) (-5.73, P = .000) and child-reported sleep problems (ISI) (-4.29, P = .005) after 16 weeks. The improvement in sleep was larger among WB adherent vs. non-adherent (between-group difference: CSHQ: -2.09, P = .038; ISI: -2.58, P =.007). Total sleep time was stable for children adherent to WB but decreased for non-adherent (between-group difference: +16.90, P = .019). CONCLUSIONS: An early response in sleep and acceptance of the WB predicted later adherence to WBs. Improvements in sleep were more likely among WB adherents vs. non-adherents. Children with ADHD may thus benefit from using WBs to handle their sleep problems.

Could nutrition status predict fatigue one week before in patients with nasopharynx cancer undergoing radiotherapy?

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy experience significant fatigue, which is frequently underestimated due to the lack of objective indicators for its evaluation. This study aimed to explore the longitudinal association between fatigue and nutrition status 1 week in advance. METHODS: From January 2021 to June 2022, a total of 105 NPC patients who received intensity-modulated radiation therapy were enrolled in the observational longitudinal study. The significant outcomes, including the Piper Fatigue Scale-12 (PFS-12), the Scored Patient-Generated Subjective Global Assessment (PG-SGA), four body composition indices, and the Hospital Anxiety and Depression Scale (HADS), were assessed weekly from pre-treatment until the completion of radiotherapy (T0-T7) to explore their relationship. RESULTS: The trajectories of PFS-12 and all dimensions for 105 participants reached a peak during the fifth week. Sensory fatigue consistently received the highest scores (T0 = 1.60 ± 2.20, T5 = 6.15 ± 1.57), whereas behavior fatigue exhibited the fastest increase over time (T0 = 1.11 ± 1.86, T5 = 5.47 ± 1.70). Higher PG-SGA scores were found to be weakly explainable for aggravating fatigue (ß = 0.02 ~ 0.04). Unlike generalized additive mixed models, marginal structural models (MSM) produced larger effect values (ß = 0.12 ~ 0.21). Additionally, body composition indices showed weakly negative relationships with fatigue in MSMs one week in advance. CONCLUSIONS: The PG-SGA may be a more accurate predictor of future-week fatigue than individual body composition indicators, particularly when HADS is controlled for as a time-dependent confounder.

Longitudinal studies of bipolar patients and their families: translating findings to advance individualized risk prediction, treatment and research.

BACKGROUND: Bipolar disorder is a broad diagnostic construct associated with significant phenotypic and genetic heterogeneity challenging progress in clinical practice and discovery research. Prospective studies of well-characterized patients and their family members have identified lithium responsive (LiR) and lithium non-responsive (LiNR) subtypes that hold promise for advancement. METHOD: In this narrative review, relevant observations from published longitudinal studies of well-characterized bipolar patients and their families spanning six decades are highlighted. DSM diagnoses based on SADS-L interviews were decided in blind consensus reviews by expert clinicians. Genetic, neurobiological, and psychosocial factors were investigated in subsets of well-characterized probands and adult relatives. Systematic maintenance trials of lithium, antipsychotics, and lamotrigine were carried out. Clinical profiles that included detailed histories of the clinical course, symptom sets and disorders segregating in families were documented. Offspring of LiR and LiNR families were repeatedly assessed up to 20 years using KSADS-PL format interviews and DSM diagnoses and sub-threshold symptoms were decided by expert clinicians in blind consensus reviews using all available clinical and research data. RESULTS: A characteristic clinical profile differentiated bipolar patients who responded to lithium stabilization from those who did not. The LiR subtype was characterized by a recurrent fully remitting course predominated by depressive episodes and a positive family history of episodic remitting mood disorders, and not schizophrenia. Response to lithium clustered in families and the characteristic clinical profile predicted lithium response, with the episodic remitting course being a strong correlate. There is accumulating evidence that genetic and neurobiological markers differ between LiR and LiNR subtypes. Further, offspring of bipolar parents subdivided by lithium response differed in developmental history, clinical antecedents and early course of mood disorders. Moreover, the nature of the emergent course bred true from parent to offspring, independent of the nature of emergent psychopathology. CONCLUSIONS: Bipolar disorders are heterogeneous and response to long-term lithium is associated with a familial subtype with characteristic course, treatment response, family history and likely pathogenesis. Incorporating distinctive clinical profiles that index valid bipolar subtypes into routine practice and research will improve patient outcomes and advance the development and translation of novel treatment targets to improve prevention and early intervention.

Impact of informal caregiving on depressive symptoms among a national cohort of men.

BACKGROUND: There is evidence that unpaid caregiving can have negative effects on the mental health of female caregivers; however, evidence of impacts on male caregivers is limited. This study addressed this gap by examining associations between becoming a caregiver and depressive symptoms among men. METHODS: We used data from waves 1-2 (2013, 2016) of the Longitudinal Study of Australian Male Health (Ten to Men). Effects of incident caregiving on depressive symptoms were estimated using augmented inverse probability treatment weighting, with adjustment for potential confounders. Incident caregiving was assessed as a binary variable (became a caregiver vs not), and depressive symptoms were measured using the Patient Health Questionnaire (moderate to severe depressive symptoms; yes, no). Main analysis was prospective, drawing on wave 1 (caregiving) and wave 2 (depressive symptoms), and sensitivity analyses modelled cross-sectional associations. RESULTS: In the main analysis, incident caregiving in wave 1 was associated with depressive symptoms in the subsequent wave, with an average treatment effect of 0.11 (95% CI 0.06, 0.17) and equating to a risk ratio of 2.03 (95% CI 1.55, 2.51). Associations were robust to several sensitivity analyses, with cross-sectional associations supporting the main prospective analyses. CONCLUSION: These results provide evidence of the association between caregiving and depressive symptoms among male caregivers. This has important implications for policy and support programmes. As we seek to shift caregiving responsibilities toward a more gender-equal distribution of care, policy must recognise that, like female caregivers, male caregivers also experience mental health impacts related to their caregiving role.

Childhood Violence, High School Academic Environment, and Adult Alcohol Use Among Latinas and Black Women: A Structural Equation Modeling Study.

OBJECTIVE: Young Latinas and Black women drink less than women of other racial/ethnic groups but experience more alcohol-related problems in midlife. This study aims to identify modifiable factors to prevent adult onset of alcohol use disorder (AUD) in this population. METHODS: Data were collected at six time points as part of the Harlem Longitudinal Development Study from 365 Latinas (47%) and Black (53%) women (mean age at time 1 = 14, standard deviation 1.3). Structural equation modeling was used to test hypothesized pathways from childhood physical and sexual abuse to AUD via depressive mood, anxiety disorders, and somatic complaints in the 20s. We also tested the moderation effect of the high school academic environment by including in the structural equation model two latent variable interaction terms between the school environment and each of the abuse variables. RESULTS: Childhood physical and sexual abuse was positively associated with depressive mood, anxiety disorders, and somatic complaints when participants were in the 20s. Depressive mood mediated childhood abuse and AUD when women were in the 30s. The high school academic environment attenuated the effect of physical, but not sexual abuse, on depressive mood (ß = -0.59, B = -9.38, 95% CI [-14.00, -4.76]), anxiety symptoms (ß = -0.61, B = -14.19, 95% CI [-21.76, -6.61]), appetite loss (ß = -0.41, B = -10.52, 95% CI [-15.61, -5.42]), and sleeplessness (ß = -0.50, B = -9.56, 95% CI [-13.95, -5.17]) in the early 20s. CONCLUSIONS: Our findings underscore the need to invest in early violence prevention interventions and in education to ensure equitable access to quality, academically oriented, and safe schools.

Hepatocyte growth factor and risk of incident stroke in Black and White Americans in the Reasons for Geographic and Racial Differences in Stroke study.

Background: Hepatocyte growth factor (HGF) is a cytokine produced in response to endothelial damage. Higher levels correlate with cardiovascular risk factors, including hypertension and diabetes. Objectives: We hypothesized that HGF is associated with stroke. Methods: The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White Americans aged ≥45 years from 2003 to 2007. In this case-cohort study, after 5.5 years of follow-up, circulating baseline HGF was measured in 557 participants with incident ischemic stroke and in a cohort random sample of 964 participants. Hazard ratios (HRs) per SD log-transformed HGF and by HGF quintile were calculated using Cox proportional hazards models adjusting for stroke risk factors and other correlates of HGF. Differences by race and sex were tested using interaction terms. Results: Median HGF was 295 (IQR, 209-402) pg/mL. HGF was higher with older age, male sex, prevalent cardiovascular disease, smoking, and warfarin use, but did not differ by race. The adjusted HR of incident ischemic stroke per SD higher baseline HGF (145 pg/mL) was 1.30 (CI, 1.00-1.70), with no difference by sex or race. HGF in the highest (>434 pg/mL) vs lowest quintile (<135 pg/mL) was associated with an adjusted HR of incident stroke of 2.12 (CI, 1.31-3.41). Conclusion: In the REGARDS study, higher HGF was associated with increased risk of incident ischemic stroke in Black and White adults, with a doubling in risk of HGF in the top quintile compared with the lowest quintile after adjusting for other stroke risk factors.

Interplay of early negative life events, development of orbitofrontal cortical thickness and depression in young adulthood.

Background: Early negative life events (NLE) have long-lasting influences on neurodevelopment and psychopathology. Reduced orbitofrontal cortex (OFC) thickness was frequently associated with NLE and depressive symptoms. OFC thinning might mediate the effect of NLE on depressive symptoms, although few longitudinal studies exist. Using a complete longitudinal design with four time points, we examined whether NLE during childhood and early adolescence predict depressive symptoms in young adulthood through accelerated OFC thinning across adolescence. Methods: We acquired structural MRI from 321 participants at two sites across four time points from ages 14 to 22. We measured NLE with the Life Events Questionnaire at the first time point and depressive symptoms with the Center for Epidemiologic Studies Depression Scale at the fourth time point. Modeling latent growth curves, we tested whether OFC thinning mediates the effect of NLE on depressive symptoms. Results: A higher burden of NLE, a thicker OFC at the age of 14, and an accelerated OFC thinning across adolescence predicted young adults' depressive symptoms. We did not identify an effect of NLE on OFC thickness nor OFC thickness mediating effects of NLE on depressive symptoms. Conclusions: Using a complete longitudinal design with four waves, we show that NLE in childhood and early adolescence predict depressive symptoms in the long term. Results indicate that an accelerated OFC thinning may precede depressive symptoms. Assessment of early additionally to acute NLEs and neurodevelopment may be warranted in clinical settings to identify risk factors for depression.

Self-rated health in old age, related factors and survival: A 20-Year longitudinal study within the Silver-MONICA cohort.

INTRODUCTION: Self-rated health (SRH) offers insights into the evolving health demographics of an ageing population. AIM: To assess change in SRH from old age to very old age and their associations with health and well-being factors, and to investigate the association between SRH and survival. METHODS: All participants in the MONICA 1999 re-examination born before 1940 (n = 1595) were included in the Silver-MONICA baseline cohort. The Silver-MONICA follow-up started in 2016 included participants in the Silver-MONICA baseline cohort aged 80 years or older. Data on SRH was available for 1561 participants at baseline with 446 of them also participating in the follow-up. The follow-up examination included a wide variety of measurements and tests. FINDINGS: Most participants rated their health as "Quite good" (54.5 %) at baseline. Over the study period, 42.6 % had stable SRH, 40.6 % had declined, and 16.8 % had improved. Changes in SRH were at follow-up significantly associated with age, pain, nutrition, cognition, walking aid use, self-paced gait speed, lower extremity strength, independence in activities of daily living, weekly physical exercise, outdoor activity, participation in organized activities, visiting others, morale, and depressive symptoms. SRH at baseline was significantly associated with survival (p < 0.05). CONCLUSION: This study demonstrates associations between changes in SRH and a multitude of health- and wellbeing-related factors, as well as a relation between survival and SRH, accentuating their relevance within the ageing population.

Heart Rate Variability, Deceleration Capacity of Heart Rate, and Death: A Veteran Twins Study.

BACKGROUND: Autonomic function can be measured noninvasively using heart rate variability (HRV), which indexes overall sympathovagal balance. Deceleration capacity (DC) of heart rate is a more specific metric of vagal modulation. Higher values of these measures have been associated with reduced mortality risk primarily in patients with cardiovascular disease, but their significance in community samples is less clear. METHODS AND RESULTS: This prospective twin study followed 501 members from the VET (Vietnam Era Twin) registry. At baseline, frequency domain HRV and DC were measured from 24-hour Holter ECGs. During an average 12-year follow-up, all-cause death was assessed via the National Death Index. Multivariable Cox frailty models with random effect for twin pair were used to examine the hazard ratios of death per 1-SD increase in log-transformed autonomic metrics. Both in the overall sample and comparing twins within pairs, higher values of low-frequency HRV and DC were significantly associated with lower hazards of all-cause death. In within-pair analysis, after adjusting for baseline factors, there was a 22% and 27% lower hazard of death per 1-SD increment in low-frequency HRV and DC, respectively. Higher low-frequency HRV and DC, measured during both daytime and nighttime, were associated with decreased hazard of death, but daytime measures showed numerically stronger associations. Results did not substantially vary by zygosity. CONCLUSIONS: Autonomic inflexibility, and especially vagal withdrawal, are important mechanistic pathways of general mortality risk, independent of familial and genetic factors.

Longitudinal Relationship Between Brain Atrophy Patterns, Cognitive Decline, and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease Explored by Orthonormal Projective Non-Negative Matrix Factorization.

Background: Longitudinal magnetic resonance imaging (MRI) has been proposed for tracking the progression of Alzheimer's disease (AD) through the assessment of brain atrophy. Objective: Detection of brain atrophy patterns in patients with AD as the longitudinal disease tracker. Methods: We used a refined version of orthonormal projective non-negative matrix factorization (OPNMF) to identify six distinct spatial components of voxel-wise volume loss in the brains of 83 subjects with AD from the ADNI3 cohort relative to healthy young controls from the ABIDE study. We extracted non-negative coefficients representing subject-specific quantitative measures of regional atrophy. Coefficients of brain atrophy were compared to subjects with mild cognitive impairment and controls, to investigate the cross-sectional and longitudinal associations between AD biomarkers and regional atrophy severity in different groups. We further validated our results in an independent dataset from ADNI2. Results: The six non-overlapping atrophy components represent symmetric gray matter volume loss primarily in frontal, temporal, parietal and cerebellar regions. Atrophy in these regions was highly correlated with cognition both cross-sectionally and longitudinally, with medial temporal atrophy showing the strongest correlations. Subjects with elevated CSF levels of TAU and PTAU and lower baseline CSF Aß42 values, demonstrated a tendency toward a more rapid increase of atrophy. Conclusions: The present study has applied a transferable method to characterize the imaging changes associated with AD through six spatially distinct atrophy components and correlated these atrophy patterns with cognitive changes and CSF biomarkers cross-sectionally and longitudinally, which may help us better understand the underlying pathology of AD.

First implantable cardiac defibrillator insertions in New South Wales, 2005-2020: an analysis of linked administrative data.

OBJECTIVES: To determine the annual numbers of first ICD insertions in New South Wales during 2005-2020; to examine health outcomes for people who first received ICDs during this period. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: All first insertions of ICDs in NSW, 2005-2020. MAIN OUTCOME MEASURES: Annual numbers of first ICD insertions, and of emergency department presentations and hospital re-admissions 30 days, 90 days, 365 days after first ICD insertions; all-cause and disease-specific mortality (to ten years after ICD insertion). RESULTS: During 2005-2020, ICDs were first inserted into 16 867 people (18.5 per 100 000 population); their mean age was 65.7 years (standard deviation, 13.5 years; 7376 aged 70 years or older, 43.7%), 13 214 were men (78.3%). The annual number of insertions increased from 791 in 2005 to 1256 in 2016; the first ICD insertion rate increased from 15.5 in 2005 to 18.9 per 100 000 population in 2010, after which the rate was stable until 2019 (19.8 per 100 000 population). Of the 16 778 people discharged alive from hospital after first ICD insertions, 54.4% presented to emergency departments within twelve months, including 1236 with cardiac arrhythmias (7.4%) and 434 with device-related problems (2.6%); 56% were re-admitted to hospital, including 1944 with cardiac arrhythmias (11.5%) and 2045 with device-related problems (12.1%). A total of 5624 people who received first ICDs during 2005-2020 (33.3%) died during follow-up (6.7 deaths per 100 person-years); the survival rate was 94.4% at one year, 76.5% at five years, and 54.2% at ten years. CONCLUSIONS: The annual number of new ICDs inserted in NSW has increased since 2005. A substantial proportion of recipients experience device-related problems that require re-admission to hospital. The potential harms of ICD insertion should be considered when assessing the likelihood of preventing fatal ventricular arrhythmia.

Quality of life in patients with nasopharyngeal carcinoma receiving IMRT vs IMPT: a multicenter prospective longitudinal study.

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT). METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL. RESULTS: Patients' symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL. CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.

Joint Trajectories of Depression and Rumination: Experiential Predictors and Risk of Nonsuicidal Self-Injury.

OBJECTIVE: Nonsuicidal self-injury (NSSI) is common in adolescence. Rumination is a key risk factor and often co-occurs with depressive symptoms. This is the first study to examine the joint longitudinal trajectories of rumination and depressive symptoms as predictors of NSSI, and the adverse experiences associated with these trajectories. METHOD: A community sample of 1,835 adolescents (55.9% male participants, 12.3 ± 0.5 years of age) completed questionnaires to assess adverse childhood experiences, rumination, depressive symptoms, and NSSI. Assessments were made 4 times over 18 months. RESULTS: A parallel process growth mixture model showed that youth with high trajectories of rumination but low trajectories of depression had moderately increased odds of NSSI (2.43-fold, 95% CI 1.53-3.91) compared with adolescents with low trajectories of both rumination and depression. Odds ratios (ORs) in adolescents with low trajectories of rumination but increasing or high trajectories of depression were similarly elevated, suggesting that high trajectories of rumination or depression were risk factors in isolation. However, odds were 10.06-fold greater (95% CI 5.68-18.02) when high trajectories of rumination occurred in tandem with high trajectories of depression. Multinomial logistic regression showed that male sex (OR 10.54, 95% CI 5.66-19.63), peer victimization (OR 2.25, 95% CI 1.72-2.96), and parental alienation (OR 1.94, 95% CI 1.46-2.57) were key determinants of membership in the highest risk group. CONCLUSION: Risk for NSSI is markedly increased in adolescents with high longitudinal trajectories of depression and rumination. Reducing exposure to peer victimization, cyber victimization, emotional abuse, parental alienation, and interparental conflict may reduce risk.

Panel Design and Optimization for Full Spectrum Flow Cytometry.

Technological advancements in fluorescence flow cytometry and an ever-expanding understanding of the complexity of the immune system have led to the development of large flow cytometry panels, reaching up to 40 markers at the single-cell level. Full spectrum flow cytometry, which measures the full emission range of all the fluorophores present in the panel instead of only the emission peaks, is now routinely used in laboratories around the world, and the demand for this technology is rapidly increasing. With the ability to use larger and more complex staining panels, optimized protocols are vital for achieving the best panel design, panel optimization, and high-dimensional data analysis outcomes. In addition, a better understanding of how to fully characterize the autofluorescence of the sample, coupled with an intelligent panel design approach, allows improved marker resolution on highly autofluorescent tissues or cells. Here, we provide optimized step-by-step protocols for full spectrum flow cytometry, covering panel design and optimization, autofluorescence evaluation and strategy selection, and methods for performing longitudinal studies.

Sleep-Related Predictors of Risk for Alcohol Use and Related Problems in Adolescents and Young Adults.

PURPOSE: Growing evidence supports sleep and circadian rhythms as influencing alcohol use and the course of alcohol use disorder (AUD). Studying sleep/circadian-alcohol associations during adolescence and young adulthood may be valuable for identifying sleep/circadian-related approaches to preventing and/or treating AUD. This paper reviews current evidence for prospective associations between sleep/circadian factors and alcohol involvement during adolescence and young adulthood with an emphasis on the effects of sleep/circadian factors on alcohol use. SEARCH METHODS: The authors conducted a literature search in PsycInfo, PubMed, and Web of Science using the search terms "sleep" and "alcohol" paired with "adolescent" or "adolescence" or "young adult" or "emerging adult," focusing on the title/abstract fields, and restricting to English-language articles. Next, the search was narrowed to articles with a prospective/longitudinal or experimental design, a sleep-related measure as a predictor, an alcohol-related measure as an outcome, and confirming a primarily adolescent and/or young adult sample. This step was completed by a joint review of candidate article abstracts by two of the authors. SEARCH RESULTS: The initial search resulted in 720 articles. After review of the abstracts, the list was narrowed to 27 articles reporting on observational longitudinal studies and three articles reporting on intervention trials. Noted for potential inclusion were 35 additional articles that reported on studies with alcohol-related predictors and sleep-related outcomes, and/or reported on candidate moderators or mediators of sleep-alcohol associations. Additional articles were identified via review of relevant article reference lists and prior exposure based on the authors' previous work in this area. DISCUSSION AND CONCLUSIONS: Overall, the review supports a range of sleep/circadian characteristics during adolescence and young adulthood predicting the development of alcohol use and/or alcohol-related problems. Although sleep treatment studies in adolescents and young adults engaging in regular and/or heavy drinking show that sleep can be improved in those individuals, as well as potentially reducing alcohol craving and alcohol-related consequences, no studies in any age group have yet demonstrated that improving sleep reduces drinking behavior. Notable limitations include relatively few longitudinal studies and only two experimental studies, insufficient consideration of different assessment timescales (e.g., day-to-day vs. years), insufficient consideration of the multidimensional nature of sleep, a paucity of objective measures of sleep and circadian rhythms, and insufficient consideration of how demographic variables may influence sleep/circadian-alcohol associations. Examining such moderators, particularly those related to minoritized identities, as well as further investigation of putative mechanistic pathways linking sleep/circadian characteristics to alcohol outcomes, are important next steps.

Impact of sitting at work on musculoskeletal complaints of German workers - results from the study on mental health at work (S-MGA).

INTRODUCTION: Sedentary behavior (including prolonged sitting) is a form of physical inactivity that has a negative impact on health, possibly including musculoskeletal complaints (MSCs). The purpose of this study was to determine the extent to which time spent sitting at work is associated with the one-year prevalence of MSCs in the neck, shoulder, upper back/thoracic spine, and lower back among workers from the Study of Mental Health in the Workplace (S-MGA). In addition, the study also examined whether leisure time, physical activity, and sex modify the relationship between occupational sitting and MSCs. METHODS: For this analysis, we used the S-MGA, a 5-year prospective study in Germany. The S-MGA is a nationwide representative employee cohort study with a baseline survey in 2012 and a follow-up survey in 2017. Sitting at work was measured using a question asked at baseline. The Nordic Musculoskeletal Questionnaire was used to determine the one-year prevalence of MSCs in the neck, shoulder, upper back, and lower back pain (yes/no). The assessment of MSCs was only conducted at the 2017 follow-up. Adjusted Poisson regression models were used to determine the association of baseline level of weekly hours spent sitting at work with MSCs during follow-up. In addition to unadjusted models, models were adjusted for demographic (age, sex, body mass index and occupational skill level), occupational (heavy lifting at work), psychological disorders and lifestyle factors (smoking status and leisure time physical activity), as well as preexisting musculoskeletal conditions reported at baseline. To examine whether the relationship between sitting time and pain was modified by sex and leisure time physical activity, the models were stratified for both these variables. RESULTS: Among the participants analyzed (n = 2,082), 49.8% were male, while 50.2% were female, and more than 60% of the study population spent over half of their working hours in a sitting position. Exposure to increased sitting at work reported at baseline was not consistently associated with 12-month prevalence of MSCs in the upper body at follow-up. However, differences in the association between occupational sitting and MSCs were dependent on the intensity of leisure time physical activity. Prevalence ratios (PRs) indicated an increased prevalence of MSC in the neck (PR = 1.46; 95% CI = 1.18-1.80) and shoulder (PR = 1.30; 95% CI = 1.03-1.64) in workers without leisure time physical activity who spent 25 to < 35 weekly working hours sitting. DISCUSSION: These findings suggest that leisure time physical activity interacts with the relationship between sitting at work and MSCs. The relationship between sitting at work and musculoskeletal pain needs further investigation, but we found indications that leisure time physical activity may counter the effects of sitting at work.