Factors associated with plans for early retirement among Ontario family physicians during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Higher numbers of family physicians (FPs) stopped practicing or retired during the COVID-19 pandemic, worsening the family doctor shortage in Canada. Our study objective was to determine which factors were associated with FPs' plans to retire earlier during the COVID-19 pandemic. METHODS: We administered two cross-sectional online surveys to Ontario FPs asking whether they were "planning to retire earlier" as a result of the pandemic during the first and third COVID-19 pandemic waves (Apr-Jun 2020 and Mar-Jul 2021). We used logistic regression to determine which factors were associated with early retirement planning, adjusting for age. RESULTS: The age-adjusted proportion of FP respondents planning to retire earlier was 8.2% (of 393) in the first-wave and 20.5% (of 454) in the third-wave. Planning for earlier retirement during the third-wave was associated with age over 50 years (50-59 years odds ratio (OR) 5.37 (95% confidence interval (CI):2.33-12.31), 60 years and above OR 4.18 (95% CI: 1.90-10.23)), having difficulty handling increased non-clinical responsibilities (OR 2.95 (95% CI: 1.79-4.94)), feeling unsupported to work virtually (OR 1.96 (95% CI: 1.19-3.23)) or in-person (OR 2.70 (95% CI: 1.67-4.55)), feeling unable to provide good care (OR 1.82 (95% CI: 1.10-3.03)), feeling work was not valued (OR 1.92 (95% CI: 1.15-3.23)), feeling frightened of dealing with COVID-19 (OR 2.01 (95% CI: 1.19-3.38)), caring for an elderly relative (OR 2.36 (95% CI: 1.69-3.97)), having difficulty obtaining personal protective equipment (OR 2.00 (95% CI: 1.16-3.43)) or difficulty implementing infection control practices in clinic (OR 2.10 (95% CI: 1.12-3.89)). CONCLUSIONS: Over 20% of Ontario FP respondents were considering retiring earlier by the third-wave of the COVID-19 pandemic. Supporting FPs in their clinical and non-clinical roles, such that they feel able to provide good care and that their work is valued, reducing non-clinical (e.g., administrative) responsibilities, dealing with pandemic-related fears, and supporting infection control practices and personal protective equipment acquisition in clinic, particularly in those aged 50 years or older may help increase family physician retention during future pandemics.

Social and circadian rhythm dysregulation and suicide: A systematic review and meta-analysis.

This systematic review of 52 studies provides a quantitative synthesis of the empirical literature on social and circadian rhythm correlates of suicidal thoughts and behaviors (STB). Small-to-medium pooled effect sizes were observed for associations between evening chronotype and STB and suicidal ideation (SI), although the pooled effect size diminished when accounting for publication bias. Three studies employed longitudinal designs and suggested eveningness was predictive of future STB, with a small-to-medium effect size. Social rhythm irregularity was also a significant correlate of STB with pooled effect sizes in the medium range. Overall circadian rhythm disruption was not associated with STB, although certain circadian rhythm metrics, including mean daytime activity, circadian rhythm sleep-wake disorder diagnosis, and actigraphy-assessed amplitude were associated with STB. Pooled effect sizes for these indices were in the medium to large range. There is a need for additional longitudinal research on actigraphy-based circadian parameters and objective markers of circadian phase (i.e., dim-light melatonin onset) to gain a clearer understanding of associations of endogenous circadian function and STB beyond that which can be captured via self-report.

Racial and ethnic trends in mental health service utilisation and perceived unmet need in the USA.

BACKGROUND: Two decades ago, the Surgeon General issued a report highlighting concerning disparities in mental healthcare among racial and ethnic minority populations. The present study characterised national trends in mental health treatment utilisation by race and ethnicity across a 13-year period. METHODS: Nationally representative data were drawn from the National Survey on Drug Use and Health from 2008 through 2020 (unweighted n=4 41 993). Trends in mental health treatment utilisation and perceived unmet treatment need among individuals with and without psychiatric illness were stratified by race and ethnicity. RESULTS: Logistic regression analyses revealed most racial/ethnic minority groups were less likely to receive treatment than white individuals, regardless of mental health status. Treatment utilisation increased among those with (annual per cent change (APC)=0.83, 95% CI=0.41 to 1.26) and without psychiatric illness (APC=1.39, 95% CI=0.53 to 2.26). Among individuals with psychiatric illness, treatment use increased among white (APC=0.88, 95% CI=0.51 to 1.24), Hispanic (APC=2.12, 95% CI=0.70 to 3.57) and black adults (APC=1.07, 95% CI=0.11 to 2.04). White (APC=1.88, 95% CI=0.86 to 2.91) and Hispanic (APC=2.45, 95% CI=0.02 to 4.93) individuals without psychiatric illness also saw increased treatment use. Although increases in perceived unmet treatment need were observed for all racial and ethnic groups except blacks and Native Americans with psychiatric illness, rates remained low across all groups. CONCLUSIONS: Although national rates of mental health treatment utilisation have risen, this was almost entirely observed among white and Hispanic individuals with and without psychiatric illness, highlighting the limited progress made towards eliminating disparities in care.

Reward sensitivity and social rhythms during goal-striving: An ecological momentary assessment investigation of bipolar spectrum disorders.

BACKGROUND: The reward/circadian rhythm model of bipolar spectrum disorders (BSDs) posits that when individuals with hypersensitive reward systems encounter reward-relevant events, they experience social and circadian rhythm disruption, leading to mood symptoms. The aim of the current study is to test an element of this theoretical model by investigating changes in social rhythms during and after an ecologically-valid reward-relevant event and evaluating whether the strength of these associations differ by trait reward sensitivity and BSD diagnostic group. METHODS: Young adults from three groups (low BSD risk with moderate reward sensitivity [MRew], high BSD risk with high reward sensitivity [HRew], and high reward sensitivity with BSD [HRew+BSD]) completed a reward responsiveness task and 20-day ecological momentary assessment study structured around a participant-specific goal occurring on day 15. Social rhythm disruption (SRD) and social rhythm regularity (SRR) were assessed daily. Multilevel models examined whether reward sensitivity and group moderated associations between study phase (baseline [days 1-5], goal-striving [days 16-20], or outcome [days 16-20]) and social rhythms. RESULTS: Participants experienced greater SRD after the goal-striving event during the outcome phase, compared to the baseline phase. The HRew+BSD group had significant decreases in SRR during the outcome phase, and this pattern differed significantly from the low-risk and high-risk groups. Greater task reward responsiveness also was associated with significant decreases in SRR during the outcome phase. LIMITATIONS: This study did not test whether social rhythm irregularity was associated with subsequent mood change. CONCLUSIONS: Participants exhibited social rhythm changes over the course of this ecologically valid goal-striving period, providing evidence for the interplay between reward-activating events and social rhythms. The HRew+BSD group showed a distinct pattern in which their social rhythms were more irregular after completing reward-relevant goal-striving that was not observed for the low-BSD risk or high-BSD risk groups. These findings provide additional support for Interpersonal and Social Rhythms Therapy.

Nonsuicidal Self-Injury in Preadolescents.

OBJECTIVES: There is a dearth of literature on the prevalence and predictors of nonsuicidal self-injury (NSSI) history and onset among preadolescent youth. This gap in the literature is significant given evidence suggesting that NSSI is a robust predictor of negative mental health outcomes, and that early onset NSSI may be associated with a more severe course of self-injurious thoughts and behaviors. This study aimed to evaluate sociodemographic characteristics, psychiatric disorders, and suicidal ideation (SI) in relation to NSSI onset and history in preadolescents. METHODS: Data were drawn from the Adolescent Brain and Cognitive Development (ABCD) study, which recruited a diverse sample of 11 875 youth aged 9 to 10 years. The primary outcome measures were lifetime history and recent onset of NSSI. Measures included sociodemographics and the K-SADS diagnostic interview assessing psychopathology and SI. RESULTS: Female sex and identifying as Black were associated with lower odds of lifetime NSSI. Identifying as a sexual minority, having unmarried parents, and a low family income were associated with higher odds of lifetime NSSI. Although depression was most predictive of NSSI history and onset, a range of internalizing and externalizing disorders, greater comorbidity, and SI also were predictive. CONCLUSIONS: Given that NSSI was associated with a range of mental health disorders and comorbidity, it may be best conceptualized as a transdiagnostic phenomenon. Findings highlight key sociodemographic and diagnostic factors that may help to direct screening efforts in preadolescents, particularly sexual minority status and depression.

Social jetlag and trajectories of mood symptoms and reward responsiveness in individuals at low-risk, high-risk, and with bipolar spectrum disorders: An ecological momentary assessment study.

A specific type of sleep disruption, social jetlag, involves an incongruence of sleep time between weekends and weekdays. This study investigated relationships between social jetlag and mood symptom lability and trajectories of daily reward responsiveness and mood symptoms. Participants (N = 130) from three groups (moderate reward sensitivity, high reward sensitivity, and high reward sensitivity with a diagnosed bipolar spectrum disorder [BSD]) were recruited from an ongoing longitudinal study based on their self-reported reward sensitivity and a diagnostic interview. For this study, they completed 20 days of ecological momentary assessment (EMA) of reward responsiveness and mood symptoms and a daily sleep diary. Social jetlag was significantly associated with differences in trajectories of depressive symptoms between groups. Specifically, greater social jetlag was associated with a greater increase in depressive symptoms over the 20 days for participants in the high reward sensitivity and BSD groups compared to the moderate reward sensitivity group. Social jetlag also was significantly associated with depressive symptom lability during the EMA period, but this finding was reduced to a trend toward significance when controlling for self-reported sleep duration. The study adds to the literature with methodological strengths including the EMA design and assessment of symptom and reward responsiveness trajectories.

Circadian, Reward, and Emotion Systems in Teens prospective longitudinal study: protocol overview of an integrative reward-circadian rhythm model of first onset of bipolar spectrum disorder in adolescence.

BACKGROUND: Bipolar spectrum disorders (BSDs) are associated with a heightened sensitivity to rewards and elevated reward-related brain function in cortico-striatal circuitry. A separate literature documents social and circadian rhythm disruption in BSDs. Recently, integrated reward-circadian models of BSDs have been proposed. These models draw on work indicating that the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. Project CREST (Circadian, Reward, and Emotion Systems in Teens) provides a first systematic test of reward-circadian dysregulation as a synergistic and dynamic vulnerability for first onset of BSD and increases in bipolar symptoms during adolescence. METHODS: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 320 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior BSD or hypomanic episode. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, participants will complete assessments of reward-relevant and social rhythm disruption life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, participants also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social reward responsiveness, and a 7-day ecological momentary assessment (EMA) period. During each EMA period, participants will complete continuous measures of sleep/wake and activity (actigraphy), a daily sleep diary, and three within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and social rhythm disruption, monetary and social reward responsiveness, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan will occur on the day before and the DLMO procedure will occur on the first evening of the 7-day EMA period. DISCUSSION: This study is an innovative integration of research on multi-organ systems involved in reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate novel pharmacological, neural, and behavioral interventions to treat, and ideally prevent, bipolar conditions.

A systematic review of associations between emotion regulation characteristics and inflammation.

Elevated inflammation is a risk factor for many psychiatric (e.g., depression) and somatic conditions (e.g., rheumatoid arthritis). Inflammation is influenced by psychosocial processes such as emotion regulation. Characterization of which emotion regulation characteristics impact inflammation could help refine psychosocial interventions aimed at normalizing health-harming inflammatory activity for individuals with psychiatric and somatic illnesses. To investigate this issue, we systematically reviewed the literature on associations between a variety of emotion regulation traits and inflammation. Out of 2816 articles identified, 38 were included in the final review. 28 (74%) found that (a) poor emotion regulation is associated with higher inflammation and/or (b) strong emotion regulation skills are associated with lower inflammation. Consistency of results differed as a function of the emotion regulation construct investigated and methodological characteristics. Results were most consistent for studies testing positive coping/social support seeking or broadly defined emotion regulation/dysregulation. Methodologically, studies testing reactivity to a stressor, adopting a vulnerability-stress framework, or using longitudinal data were most consistent. Implications for integrated, transdiagnostic psychoimmunological theories are discussed, as well as recommendations for clinical research.

An examination of bidirectional associations between physical activity and mood symptoms among individuals diagnosed and at risk for bipolar spectrum disorders.

OBJECTIVES: Activation, a construct including energy and activity, is a central feature of Bipolar Spectrum Disorders (BSDs). Prior research found motor activity is associated with affect, and this relationship may be stronger for individuals with BSDs. The aims of this study were to investigate bidirectional relationships between physical activity and mood and evaluate whether bipolar risk status moderated potential associations. METHODS: Young adults at low-risk, high-risk, and diagnosed with BSD participated in a 20-day EMA study in which they wore an actiwatch to measure physical activity and sleep/wake cycles. They also reported depressive and hypo/manic symptoms three times daily. Multilevel linear models were estimated to examine how bipolar risk group moderated bidirectional relationships between physical activity and mood symptoms at within-day and between-day timescales. RESULTS: Physical activity was significantly associated with subsequent mood symptoms at the within-day level. The relationship between physical activity and depressive symptoms was moderated by BSD risk group. An increase in physical activity resulted in a greater reduction of depressive symptoms for the BSD group compared to the low-risk and high-risk groups. CONCLUSIONS: Interventions targeting activity like behavioral activation may improve residual inter-episode mood symptoms.

The relationship between physical activity states and depressive symptoms: Using ambulatory assessment to characterize day-to-day associations among individuals with and without bipolar spectrum disorder.

INTRODUCTION: The role of activation in the pathogenesis of bipolar spectrum disorders (BSD) is of growing interest. Physical activity is known to improve mood, but it is unclear whether low activity levels contribute to inter-episode depressive symptoms observed in BSD. This study examined whether sedentary and vigorous activity, as well as the timing of the activity, were differentially associated with next-day depressive symptoms for individuals at low risk for BSD, high-risk for BSD, and diagnosed with BSD. METHODS: Young adults (n = 111, ages 18-27) from three groups (low BSD risk, high BSD risk, and BSD diagnosis), participated in a 20-day ecological momentary assessment study. Physical activity was measured via wrist actigraphy counts. The percentage of time awake spent in sedentary, light, moderate, and vigorous activity states was calculated, as was the percentage of morning hours and evening hours in each activity state. Multilevel models examined whether the BSD risk group moderated associations between sedentary and vigorous activity and depressive symptoms, which were assessed three times daily. RESULTS: There were no between-group differences in time spent in each activity state, nor were there main effects of sedentary or vigorous activity on depression. Increased time spent engaging in vigorous activity was associated with a greater reduction in subsequent depressive symptoms for the BSD group. An increase in the evening, but not morning, vigorous activity was significantly associated with a reduction in subsequent depressive symptoms for the BSD group after controlling for chronotype. CONCLUSIONS: Interventions targeting physical activity may effectively help regulate inter-episode mood disturbances in BSD.

Prevalence and Correlates of Suicide and Nonsuicidal Self-injury in Children: A Systematic Review and Meta-analysis.

Importance: Considerably less is known about self-injurious thoughts and behaviors (SITBs) in preadolescence than older age groups, owing partly to the common view that young children are incapable of suicidal thoughts. Yet, preadolescent suicide has increased in recent years and is now the fifth leading cause of death in this age group, leading the National Institute of Mental Health to identify it as a priority for research and intervention. Objective: To assess prevalence estimates of preadolescent SITBs, identify correlates of these outcomes, and conduct head-to-head comparisons of preadolescent and adolescent SITBs in terms of associated characteristics. Data Sources: MEDLINE, PsycINFO, and Embase were systematically searched from inception through December 23, 2021, for studies on the prevalence and correlates of preadolescent SITBs. The search was restricted to English language publications and peer-reviewed journals. Study Selection: Two reviewers independently identified studies providing data on prevalence and correlates of preadolescent SITBs. Data Extraction and Synthesis: Two reviewers independently extracted data from each study, and the Joanna Briggs Institute Checklist for Prevalence Studies was used to assess study quality. Pooled prevalence and Cohen d were derived from random-effects meta-analyses. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Main Outcomes and Measures: Prevalence and correlates of suicidal ideation, suicide attempts, suicide deaths, and nonsuicidal self-injury among preadolescents. Results: Fifty-eight studies with 626 486 590 individuals were included. Lifetime prevalence of suicide in the general population was 0.79 per 1 million children. Prevalence for lifetime suicidal thoughts, suicide attempts, and nonsuicidal self-injury among preadolescents were 15.1%, 2.6%, and 6.2%, respectively, in community samples. These data suggest that approximately 17.0% of preadolescents with suicidal ideation transition to attempting suicide. Across several analyses, male individuals appear more likely to have SITBs in preadolescence than adolescence. Correlate data were modest for SITBs other than suicidal ideation, but among specific disorders, attention-deficit/hyperactivity disorder (suicidal ideation: d = 0.54 [95% CI, 0.34-0.75]) and depression (suicidal ideation: d = 0.90 [95% CI, 0.71-1.09]; suicide attempts: d = 0.47 [95% CI, 0.26-0.68]) emerged as the strongest correlates. Among interpersonal factors, child maltreatment (suicidal ideation: d = 2.62 [95% CI, 1.56-3.67]) and parental support (suicidal ideation: d = -0.34 [95% CI, -0.46 to -0.22]) yielded the largest effect sizes. Conclusions and Relevance: In this systematic review anda meta-analysis, although preadolescent suicide deaths were rare, other SITB types occur with concerning frequency. Male individuals were at greater risk for SITBs in preadolescence relative to adolescence. Attention-deficit/hyperactivity disorder, child maltreatment, and parental support were especially relevant to suicidal ideation, as well as depression for suicidal thoughts and behaviors, in this age group. Further study, especially of SITBs other than suicidal ideation, is needed.

Flecainide poisoning and prolongation of elimination due to alkalinization.

BACKGROUND: Flecainide is a 1C antidysrhythmic that is primarily used for ventricular tachycardia or premature ventricular contractions when other treatment is ineffective. It has a very narrow therapeutic window which may cause death in a double dose and requires inpatient initiation for cardiac monitoring. Despite established pharmacokinetic data from flecainide in therapeutic dosing, there is negligible data on flecainide toxicokinetics after an intentional overdose. Due to the inherent differences in pharmacokinetic and toxicokinetic principles, rarely can the peak effect or elimination half-life accurately be applied to the poisoned patient after an overdose. In overdose, flecainide can cause a variety of fatal dysrhythmias which may require sodium bicarbonate for stabilization but also may reduce the renal elimination of flecainide, meaning the life-saving treatment may prolong the time of toxicity. CASE REPORT: We present a case of an acute ingestion of flecainide with a known time of ingestion and known amount of ingestion who experienced subsequent life-threatening effects which required endotracheal intubation, sodium bicarbonate, aggressive electrolyte repletion, and multiple days in an intensive care unit. RESULTS: Serial serum and urine samples revealed a prolonged toxic serum concentration of flecainide. CONCLUSION: These results demonstrate the change in elimination kinetics of flecainide in the setting of urinary alkalization which is evident through prolonged morphologic changes present on serial electrocardiograms.

Extended survival of a premature infant with a postnatal diagnosis of complete triploidy.

Triploidy is a common chromosomal abnormality that usually results in spontaneous abortion. Liveborn infants usually die within hours or days of birth. We present the case of a female infant born at 30 weeks and 5 days of gestation who received a late postnatal diagnosis of complete triploidy. She had severe intrauterine growth restriction and postnatal findings of multiple facial and limb anomalies. Genetic testing was sent shortly after birth, and the baby had an uneventful neonatal admission, requiring low-level respiratory and feeding support. Following a diagnosis of complete triploidy, she was transferred to a hospice and died on day 36 of life. There are currently 12 other reported cases of survival beyond 30 days. This case adds to the known cohort and highlights the importance of genetic testing in premature neonates with congenital anomalies in order to guide ceiling of care discussions and advocate for quality of life.

Primary Care Continuity and Wait Times to Receiving Breast Cancer Chemotherapy: A Population-Based Retrospective Cohort Study Using CanIMPACT Data.

(1) Background: Wait times to chemotherapy are associated with morbidity and mortality in breast cancer patients; however, it is unclear how primary care physician (PCP) continuity impacts these wait times, or whether this association is different in immigrants, who experience cancer care inequities. We assessed the association between PCP continuity and the contact-to-chemotherapy interval (wait time from when a patient first presents to healthcare to the first day of receiving breast cancer chemotherapy), with a specific look at the immigrant population. (2) Methods: Population-based, retrospective cohort study of women who were diagnosed with stage I-III breast cancer in Ontario who received surgery and adjuvant chemotherapy. We used quantile regression at the median and 90th percentile to quantify the effect of PCP continuity on the contact-to-chemotherapy interval, performing a separate analysis on the immigrant population. (3) Results: Among 12,781 breast cancer patients, including 1706 immigrants, the median contact-to-chemotherapy interval (126 days) was 3.21 days shorter (95% confidence interval (CI) 0.47-5.96) in symptom-detected patients with low PCP continuity, 10.68 days shorter (95% CI 5.36-16.00) in symptom-detected patients with no baseline PCP visits and 17.43 days longer (95% CI 0.90-34.76) in screen-detected immigrants with low PCP continuity compared to the same groups with high PCP continuity. (4) Conclusions: Higher PCP continuity was not associated with a change in the contact-to-chemotherapy interval for most of our study population, but was associated with a marginally longer interval in our symptom-detected population and a shorter contact-to-chemotherapy interval in screen-detected immigrants. This highlights the importance of PCP continuity among immigrants with positive screening results. Additionally, having no PCP visits at baseline was associated with a shorter contact-to-chemotherapy interval in symptom-detected patients.

Prevalence and correlates of suicidal ideation and suicide attempts in preadolescent children: A US population-based study.

The present study evaluated sociodemographic and diagnostic predictors of suicidal ideation and attempts in a nationally representative sample of preadolescent youth enrolled in the Adolescent Brain Cognitive Development Study. Rates and predictors of psychiatric treatment utilization among suicidal youth also were examined. Eleven thousand eight hundred and seventy-five 9- and 10-year-old children residing in the United States were assessed. Children and their parents/guardians provided reports of children's lifetime history of suicidal ideation, suicide attempts, and psychiatric disorders. Parents also reported on sociodemographic characteristics and mental health service utilization. Multivariate logistic regression analyses were employed to evaluate sociodemographic and diagnostic correlates of suicidal ideation, suicide attempts among youth with suicidal ideation, and treatment utilization among youth with suicidal ideation and suicide attempts. Lifetime prevalence rates were 14.33% for suicidal ideation and 1.26% for suicide attempts. Youth who identified as male, a sexual minority, or multiracial had greater odds of suicidal ideation, and sexual minority youth and youth with a low family income had greater odds of suicide attempts. Comorbid psychopathology was associated with higher odds of both suicidal ideation and suicide attempts. In youth, 34.59% who have suicidal ideation and 54.82% who had attempted suicide received psychiatric treatment. Treatment utilization among suicidal youth was lower among those who identified as female, Black, and Hispanic. Suicidal ideation and attempts among preadolescent children are concerningly high and targeted assessment and preventative efforts are needed, especially for males, racial, ethnic, and sexual minority youth, and those youth experiencing comorbidity.

Targeting microRNA-mediated gene repression limits adipogenic conversion of skeletal muscle mesenchymal stromal cells.

Intramuscular fatty deposits, which are seen in muscular dystrophies and with aging, negatively affect muscle function. The cells of origin of adipocytes constituting these fatty deposits are mesenchymal stromal cells, fibroadipogenic progenitors (FAPs). We uncover a molecular fate switch, involving miR-206 and the transcription factor Runx1, that controls FAP differentiation to adipocytes. Mice deficient in miR-206 exhibit increased adipogenesis following muscle injury. Adipogenic differentiation of FAPs is abrogated by miR-206 mimics. Using a labeled microRNA (miRNA) pull-down and sequencing (LAMP-seq), we identified Runx1 as a miR-206 target, with miR-206 repressing Runx1 translation. In the absence of miR-206 in FAPs, Runx1 occupancy near transcriptional start sites of adipogenic genes and expression of these genes increase. We demonstrate that miR-206 mimicry in vivo limits intramuscular fatty infiltration. Our results provide insight into the underlying molecular mechanisms of FAP fate determination and formation of harmful fatty deposits in skeletal muscle.

The effect of comorbidity on primary care use during breast cancer chemotherapy: a population-based retrospective cohort study using CanIMPACT data.

BACKGROUND: Patients with breast cancer visit their primary care physicians (PCPs) more often during chemotherapy than before diagnosis, but the reasons are unclear. We assessed the association between physical comorbidities and mental health history (MHH) and the change in PCP use during adjuvant breast cancer chemotherapy. METHODS: We conducted a population-based, retrospective cohort study using data from the Canadian Team to Improve Community-Based Cancer Care along the Continuum (CanIMPACT) project. Participants were women 18 years of age and older, who had received a diagnosis of stage I-III breast cancer in Ontario between 2007 and 2011 and had received surgery and adjuvant chemotherapy. We used difference-in-difference analysis using negative binomial modelling to quantify the differences in the 6-month rate of PCP visits at baseline (the 24-month period between 6 and 30 months before diagnosis) and during treatment (the 6 months from start of chemotherapy) between physical comorbidity and MHH groups. RESULTS: Among 12 781 participants, the 6-month PCP visit rate increased during chemotherapy (mean 2.3 visits at baseline, 3.4 visits during chemotherapy). Patients with higher physical comorbidity levels or MHH visited their PCPs 4.2 or 1.7 more times, respectively, over 6 months compared to those with low physical comorbidity or no MHH at baseline and 2.5 or 1.1 more times, respectively, over 6 months during treatment. During treatment, the adjusted 6-month rate of PCP visits more than doubled in the group with the fewest physical comorbidities or no MHH compared with baseline (rate ratio 2.52, 95% confidence interval [CI] 2.43-2.61). This increase was lower in those with MHH (rate ratio 1.81, 95% CI 1.68-1.96) and in the highest physical comorbidity group (rate ratio 1.16, 95% CI 1.07-1.28). INTERPRETATION: Patients with breast cancer who have more physical comorbidities and MHH have a higher frequency of PCP visits during adjuvant chemotherapy but lower absolute and relative increases in visits compared with baseline. Therefore, PCPs can expect to see their patients with fewer physical comorbidities and no MHH more often during chemotherapy. Primary care physicians can plan for their patients with high physical comorbidity levels and MHH to continue having frequent appointments while they undergo chemotherapy, and they can expect their patients with low physical comorbidity levels and no MHH to increase the frequency of their visits during chemotherapy, and should be prepared to provide breast cancer-related care to these patients.

Suicidal thoughts and behaviors in preadolescents: Findings and replication in two population-based samples.

INTRODUCTION: Given increasing concern in suicide in preadolescent children, this study aimed to characterize and identify potential indicators of risk for suicidal ideation (SI) and suicide attempts (SAs) in this population. METHODS: Data were drawn from two population-based samples of preadolescents: the 2007 and 2010 Minnesota Student Survey and analyses were restricted to 11- and 12-year-olds. Sociodemographic characteristics, childhood maltreatment, parental relations, peer relations, and school climate were examined in relation to past-year SI and SA. To examine correlates of SI, unconfounded by risk for SA, individuals with a history of SA were excluded from SI analyses. Correlates of SA were examined among individuals with past-year SI. Logistic regression analyses were conducted with past-year SI and SA as criterion variables. RESULTS: Results from the 2007 and 2010 data sets were highly consistent. The prevalence of past-year SI was 9.28% and 9.25% in 2007 and 2010, respectively. Of the total sample, 1.90% and 1.87% reported a past-year SA (17.00% and 16.78% of those with past-year SI). Overall, effect sizes were generally modest to medium. The strongest effects were observed for sexual and physical abuse, parental support, and perceived safety at school (ps < .001). In multivariate analyses of SI and SA, sexual and physical abuse had the largest effect sizes (ORSI = 2.18 [95% CI = 1.90-2.51] to 2.96 [95% CI = 2.69-3.26]; ORSA = 1.55 [95% CI = 1.29-1.86] to 2.26 [95% CI = 1.82-2.80]). CONCLUSIONS: SI and SA occur at a concerning rate among preadolescent children. Screening for childhood sexual and physical abuse may be important for identifying those at risk for these clinical outcomes.

Comorbidity and patterns of familial aggregation in attention-deficit/hyperactivity disorder and bipolar disorder in a family study of affective and anxiety spectrum disorders.

The aim of this study is to examine the familial aggregation of Attention-deficit/hyperactivity disorder (ADHD) and its cross-transmission with bipolar disorder (BD) in a community-based family study of mood spectrum disorders. A clinically-enriched community sample of 562 probands recruited from the greater Washington, DC metropolitan area and their 698 directly interviewed relatives were included in analyses. Inclusion criteria were English speaking and consent to contact at least two first-degree relatives. Standard family study methodology was used and DSM-IV classified mental disorders were ascertained through a best-estimate procedure based on direct semi-structured interviews and multiple family history reports. There was specificity of familial aggregation of both bipolar I disorder (BD I) and bipolar II disorder (BD II) (i.e., BD I OR = 6.08 [1.66, 22.3]; BD II OR = 2.98 [1.11, 7.96]) and ADHD (ADHD OR = 2.13 [1.16, 3.95]). However, there was no evidence for cross-transmission of BD and ADHD in first degree relatives (i.e., did not observe increased rates of BD in relatives of those with ADHD and vice versa; all ps > 0.05). The specificity of familial aggregation of ADHD and BD alongside the absence of shared familial risk are consistent with the notion that the comorbidity between ADHD and BD may be attributable to diagnostic artifact, could represent a distinct BD suptype characterized by childhood-onset symptoms, or the possibility that attention problems serve as a precursor or consequence of BD.

Clues beyond the lung: an unusual diagnosis in an infant with chronic lung disease.

It is important to consider alternative diagnoses when a common respiratory condition presents with atypical features. In this patient, subtle systemic signs and an unusual clinical course hinted at an unexpected aetiology. http://bit.ly/2webytn.