Association between psychosocial factors and co-morbid cigarette smoking and alcohol use in a population experiencing homelessness.

The prevalence of combustible cigarette smoking in populations experiencing homelessness in the United States is five times that of the general population. The psychosocial well-being of persons who smoke and experience homelessness is poorer if such persons also use alcohol heavily. The PTQ2 study was a randomized clinical trial among persons experiencing homelessness who were also current smokers and heavy alcohol consumers. Secondary data analysis of the PTQ2 baseline data was conducted to examine associations among psychosocial variables (anxiety, depression, hopelessness, social network size), heaviness of smoking (cigarettes/day) and alcohol consumption (drinking days/month), and duration and frequency of homelessness. Among the 420 participants, the majority were male (75%), black (70%) and non-Hispanic (94%) with a mean age of 46.6 years (SD = 11.6).  Bivariate analyses show that heaviness of smoking was positively correlated with social network size (r = 0.16, p = .001). Heaviness of drinking was positively correlated with the MINI anxiety score (r = 0.13, p = .009) and marijuana use (median total number of drinks in past 30 days among those who used marijuana in past 30 days vs. did not use: 50 vs. 24, p < .0001), and associated with frequency of homelessness (median total number of drinks in past 30 days among those experiencing homelessness once vs. >1 time: 30 vs. 44, p = .022). The findings highlight the psychosocial factors that warrant consideration when addressing heavy smoking and alcohol consumption in persons experiencing homelessness.

Low-density lipoprotein subclasses over the menopausal transition and risk of coronary calcification and carotid atherosclerosis: the SWAN Heart and HDL ancillary studies.

OBJECTIVE: Perimenopausal women experience a steep increase in low-density lipoprotein cholesterol (LDL-C) that is related to a higher risk of carotid plaque later in life. Low-density lipoprotein subclasses have been linked to cardiovascular diseases beyond LDL-C, promising a better risk stratification. We aim to characterize changes in LDL subclasses and assess their associations with presence of coronary artery calcium (CAC score ≥10) and carotid intima-media thickness (cIMT) over the menopausal transition (MT) and by menopause stage. METHODS: Nuclear magnetic resonance spectroscopy LDL subclasses were measured for a maximum of five time points. Coronary artery calcification and cIMT were measured for a maximum of two time points. LOESS (locally weighted regression with scatter smoothing) plots, linear mixed-effects models, and generalized estimating equations were used for analyses. RESULTS: The study included 471 women (baseline: age, 50.2 ± 2.7 years; 79.0% premenopausal/early perimenopausal), of whom 221 had data on CAC or cIMT. Low-density lipoprotein subclasses increased over the MT, whereas intermediate density-lipoprotein particles declined. In adjusted models, higher total LDL particles (LDL-P) and apolipoprotein B were associated with greater CAC prevalence and greater cIMT. Although none of the associations were modified by menopause stage, higher LDL-C, apolipoprotein B, and total LDL-P were associated with greater cIMT during the perimenopause or postmenopause stages, whereas higher LDL-C and small LDL-P were associated with greater CAC prevalence, mainly during perimenopause. CONCLUSIONS: During the MT, women experience significant increases in LDL subclasses found to be related to greater cIMT levels and CAC prevalence. Whether these changes could better predict future risk of hard cardiovascular disease events beyond LDL-C remains a research question to address.

Associations of prenatal and postnatal exposure to perfluoroalkyl substances with pubertal development and reproductive hormones in females and males: The HOME study.

BACKGROUND: Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce. OBJECTIVES: We examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years. METHODS: We studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003-2006). We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and females) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture. RESULTS: In females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adolescent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males. CONCLUSIONS: We observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

Integrated smoking cessation and mood management following acute coronary syndrome: Protocol for the post-acute cardiac event smoking (PACES) trial.

BACKGROUND: Approximately 400,000 people who smoke cigarettes survive Acute Coronary Syndrome (ACS; unstable angina, ST and non-ST elevation myocardial infarction) each year in the US. Continued smoking following ACS is an independent predictor of mortality. Depressed mood post-ACS is also predictive of mortality, and smokers with depressed mood are less likely to abstain from smoking following an ACS. A single, integrated treatment targeting depressed mood and smoking could be effective in reducing post-ACS mortality. METHOD/DESIGN: The overall aim of the current study is to conduct a fully powered efficacy trial enrolling 324 smokers with ACS and randomizing them to 12 weeks of an integrated smoking cessation and mood management treatment [Behavioral Activation Treatment for Cardiac Smokers (BAT-CS)] or control (smoking cessation and general health education). Both groups will be offered 8 weeks of the nicotine patch if medically cleared. Counseling in both arms will be provided by tobacco treatment specialists. Follow-up assessments will be conducted at end-of-treatment (12-weeks) and 6, 9, and 12 months after hospital discharge. We will track major adverse cardiac events and all-cause mortality for 36 months post-discharge. Primary outcomes are depressed mood and biochemically validated 7-day point prevalence abstinence from smoking over 12 months. DISCUSSION: Results of this study will inform smoking cessation treatments post-ACS and provide unique data on the impact of depressed mood on success of post-ACS health behavior change attempts. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03413423. Registered 29 January 2018. https://beta. CLINICALTRIALS: gov/study/NCT03413423 .

Sharing Perspectives in African American Communities to Reduce Stroke Risk Through Community Listening Circles.

PURPOSE: To build trust and explore community perception on stroke disparities as well as barriers and strengths to stroke prevention. DESIGN: Mixed methods study. METHODS: A convenience sample (n = 54) of African Americans responded to questionnaires and participated in focus groups. FINDINGS: Although a majority of participants had some knowledge of stroke warning signs and risk factors, there were misconceptions identified through the Community Listening Circles (CLCs). Misconceptions about stroke were identified. Six key themes emerged. CONCLUSIONS: Focus groups provided a better understanding of stroke perception. CLINICAL EVIDENCE: Community health nurses may be able to use this information to provide care appropriately.

Congenital Hypothyroidism: Screening and Management.

ABSTRACT: Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally. Seventy percent of neonates worldwide do not undergo NBS.The initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism.Newborn screening alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

Psychological measures of stress and biomarkers of inflammation, aging, and endothelial dysfunction in breast cancer survivors on aromatase inhibitors.

The use of aromatase inhibitors (AIs) is associated with higher rates of cardiovascular events and lower endothelial function in breast cancer survivors. Psychosocial stress is associated with higher levels of inflammatory and aging markers, and lower endothelial function in otherwise healthy subjects. These associations among breast cancer survivors on AIs are not well defined. A cross-sectional study of 30 breast cancer survivors on AIs was performed to assess the associations between self-reported scores of psychosocial measures of depression, anxiety, and stress assessed by validated questionnaires with markers of inflammation (CRP; IL-6; IL-18), aging (p16INK4a), and endothelial function (ICAM-1, EndoPAT ratio). Significant positive correlations were observed between psychosocial measures and inflammatory markers including CRP, IL-6, and ICAM-1. However, no psychosocial scores were related to endothelial function or gene expression of the aging biomarker p16INK4a. Overall, survivors had endothelial dysfunction with reduced EndoPAT ratios. Psychosocial stress is associated with greater inflammation in breast cancer survivors on AIs, corroborating previous studies in cancer-free populations. The lack of association between psychosocial stress and either endothelial function or aging biomarkers could be due to the already low endothelial function and accelerated aging in our cohort of breast cancer survivors on AIs, though our small sample size limits conclusions. Further work in a larger and more diverse cohort of patients is needed to further understand the relationships among inflammation, aging and endothelial function in breast cancer survivors.

Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.

OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer. METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer. RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1. CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.

Reduced-Intensity Conditioning Mitigates Risk for Primary Ovarian Insufficiency but Does Not Decrease Risk for Infertility in Pediatric and Young Adult Survivors of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many pediatric malignant and nonmalignant conditions. Gonadal insufficiency or infertility is present in almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. Reduced-intensity conditioning (RIC) regimens are being increasingly used in medically fragile patients or in patients with nonmalignant diagnoses to limit the toxicities associated with HSCT; however, the short-term and long-term gonadal toxicity of RIC regimens in pediatric and young adult survivors remains unknown. In this study, we compared the prevalence of gonadal insufficiency and infertility among pubertal and postpubertal pediatric and young adult survivors of HSCT who received a RIC regimen versus those who received a MAC regimen. Twenty-three females (RIC, n = 8; MAC, n = 15) and 35 males (RIC, n = 19; MAC, n = 16) were included in this single-center, retrospective cross-sectional study. Eligible patients were those with available laboratory results who were ≥1 year post-HSCT, age <40 years, and pubertal or postpubertal as assessed by an endocrinologist. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels were measured in females, and FSH, LH, total testosterone, and inhibin B (InhB) levels were measured in males. Twenty-one males (RIC, n = 11; MAC, n = 10) underwent semen analysis through a separate consent. Parametric and nonparametric analyses were undertaken to compare the RIC and MAC groups. Female patients who received RIC were less likely than those who received MAC to develop primary ovarian insufficiency, as demonstrated by elevated FSH (P = .02) and low estradiol (P = .01) or elevated LH (P = .09). Most females in the RIC (75%) and MAC (93%) groups had low AMH levels, indicating low or absent ovarian reserve, with no significant difference between the groups (P = .53). In males, there were no significant differences between the 2 groups in the prevalence of abnormal FSH, LH, testosterone, or InhB levels. Ten of 11 RIC males (91%) and 10 of 10 MAC males (100%) had azoospermia or oligospermia, at a median time to semen analysis from HSCT of 3.7 years (range, 1.3 to 12.2 years). RIC may pose less risk than MAC for primary ovarian insufficiency among female survivors of HSCT; however, both female and male recipients of either RIC or MAC regimens are at high risk for infertility. In the largest reported series of semen analyses of pediatric and young adult male recipients of RIC, azoospermia or oligospermia was found in nearly all (91%) RIC survivors. All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve fertility in patients undergoing either RIC or MAC.

Personal Health Literacy and Life Simple 7: The Multi-Ethnic Study of Atherosclerosis.

Background: Personal Health literacy (PHL) is essential in cardiovascular risk management. Hindrances in PHL can lead to poor cardiovascular outcomes. Purpose: To investigate whether limited PHL is associated with lower likelihoods of i) overall cardiovascular health and ii) individual cardiovascular health components as defined by the American Heart Association's Life Simple (LS7). Methods: Multi-Ethnic Study of Atherosclerosis participants (N=3719; median age[range]: 59[45-84]) completed a PHL questionnaire in 2016-2018. PHL was classified as limited (score ≥10) or adequate (score <10). LS7 components were measured in 2000-2002. Robust Poisson regression was employed to compute prevalence ratios and 95% confidence intervals (PR[95%CI]) of LS7 measures. Results: 14.7% of participants had limited PHL. Limited PHL was associated with lower likelihoods of optimal LS7 (0.69[0.50, 0.95], p=0.02) and average LS7 (0.95[0.88, 1.02], p=0.15) after adjustment. Limited PHL was significantly associated with a 7% lower likelihood of ideal fasting blood glucose level after adjustment (0.93[0.89, 0.98], p<0.01). Discussion: Limited PHL was modestly associated with suboptimal cardiovascular health and elevated blood glucose, independent of income and education. Translation to Health Education Practice: Health educators and providers should equitably address PHL barriers to improve cardiovascular management and quality of care for patients and communities.

Psychosocial predictors of fear of cancer recurrence in a cohort of gynecologic cancer survivors.

OBJECTIVE: To describe fear of cancer recurrence in a cohort of women with gynecologic cancers and to identify psychosocial predictors of elevated fear of recurrence. METHODS: Survey data from an ongoing cohort study of gynecologic cancer survivors were used (n = 154). Relationships between fear of cancer recurrence measured by the 6-item Cancer Worry Scale in the most recent survey and psychosocial factors (cancer-related distress, depression, anxiety, hopelessness, and posttraumatic growth) assessed 6-18 months prior were examined using univariate and multivariate linear regression models, adjusting for age, cancer stage, cancer type, and time since diagnosis. RESULTS: Most participants were ≥60 years old, diagnosed with early-stage cancer, and 2-5 years post-diagnosis. The mean score on the Cancer Worry Scale was 10.31 (SD = 3.01), and 46 individuals (30.0%) scored ≥12, indicating high fear of recurrence. In univariate analyses, greater distress (p = 0.007), anxiety (p = 0.006), hopelessness (p = 0.007), and posttraumatic growth (p = 0.0006) were significantly associated with higher scores on the Cancer Worry Scale. The associations of hopelessness and posttraumatic growth with higher Cancer Worry Scale scores remained significant after adjustment for covariates. CONCLUSIONS: Fear of recurrence is frequent among gynecologic cancer survivors. Women who reported more distress, hopelessness, anxiety and, surprisingly, more post-traumatic growth reported more fear. These results contribute to our understanding of which cancer survivors are most at risk of elevated fear of recurrence and highlight the importance of continued focus on psychosocial well-being among cancer survivors.

Gender Distribution of Authors of Evaluation Letters for Promotion at One Medical School.

PURPOSE: Women remain underrepresented in key leadership positions and advanced ranks in academic medicine. This study examines the numbers of men and women letter writers for promotion candidates during a 5-year period across departments, tracks, ranks, and candidate gender. METHOD: A descriptive study characterized the gender of evaluation letter writers for candidates for promotion to associate or full professor at the University of Minnesota Medical School between 2015 and 2020. Letter writer and candidate gender were characterized by self-identified pronouns in the faculty biography or dossier. Letter writer gender was described by candidate department, promotion track, rank, terminal degree, and gender. RESULTS: Among 299 candidates for promotion, 172 (58%) were men and 127 (42%) were women; dossiers included 3,995 evaluation letters. Across all years, men wrote more letters than women (external letters, range, 69% in 2019-2020 to 75% in 2015-2016; internal letters, range, 67% in 2018-2019 to 77% in 2015-2016). Candidates in the family medicine and pediatrics departments had the highest percentages of letters written by women (44% and 40%, respectively). No differences were found in the number of women letter writers by candidate promotion track; however, differences were found by candidate rank (associate professor, 30%; full professor, 23%) and terminal degree (MD/DO, 25%; PhD, 33%; MD-PhD, 20%). Regardless of candidate gender, most evaluation letters were written by men. Women candidates had 15% to 20% more letters authored by women than men candidates (34%-40% vs 18%-23%). CONCLUSIONS: The gender pattern of letter writers may reflect implicit biases regarding gender and perceived leadership status, expertise, and success. Adopting policies that promote or require gender diversity among letter writers for promotion candidates may provide an opportunity to encourage faculty to seek diverse networks and recognize the achievements of women faculty.

Smoking reduction among homeless smokers in a randomized controlled trial targeting cessation.

INTRODUCTION: Homeless populations have high rates of smoking and unique barriers to quitting. General cessation strategies have been unsuccessful in this population. Smoking reduction may be a good intermediate goal. We conducted a secondary analysis to identify predictors of smoking reduction in a cohort of homeless smokers enrolled in a 26-week randomized clinical trial (RCT) targeting smoking cessation. METHODS: Data are from an RCT comparing motivational interviewing counseling plus nicotine replacement therapy (NRT) to brief advice to quit (standard care) plus NRT among homeless smokers. Using bivariate analyses and multinomial logistic regression, we compared demographics, health and psychosocial variables, tobacco use, substance use, and NRT adherence among those who reported: quitting; reducing smoking by 50-99%; and not reducing smoking by 50%. RESULTS: Of 324 participants who completed 26-week follow-up, 18.8% and 63.9% self-reported quitting and reducing, respectively. Compared to those who did not reduce smoking, participants reporting reducing indicated higher baseline cigarette use (OR=1.08; CI:1.04-1.12) and menthol use (OR=2.24; CI:1.05-4.77). Compared to participants who reduced, participants reporting quitting were more likely to be male (OR=1.998; CI:1.00-3.98), experience more housing instability (OR=1.97; CI:1.08-3.59), indicate higher importance of quitting (OR=1.27; CI:1.041.55), have higher NRT adherence (OR=1.75; CI:1.00-3.06), and lower odds of reported illicit drug use (OR=0.48; CI:0.24-0.95). CONCLUSIONS: Over half of participants reduced smoking by at least 50%, indicating reduction is feasible among homeless smokers. Further research is required to understand the impact of reduction on future cessation attempts in homeless smokers. This study shows that reduction is achievable and may be a valid intermediate goal.

The implementation of a smoking cessation and alcohol abstinence intervention for people experiencing homelessness.

BACKGROUND: In the United States, eighty percent of the adult homeless population smokes cigarettes compared to 15 percent of the general population. In 2017 Power to Quit 2 (PTQ2), a randomized clinical trial, was implemented in two urban homeless shelters in the Upper Midwest to address concurrent smoking cessation and alcohol treatment among people experiencing homelessness. A subset of this study population were interviewed to assess their experiences of study intervention. The objective of this study was to use participants' experiences with the intervention to inform future implementation efforts of combined smoking cessation and alcohol abstinence interventions, guided by the Consolidated Framework for Implementation Research (CFIR). METHODS: Qualitative semi-structured interviews were conducted with 40 PTQ2 participants between 2016-2017 and analyzed in 2019. Interviews were audio-recorded, transcribed, and analyzed using a socially constructivist approach to grounded theory. RESULTS: Participants described the PTQ2 intervention in positive terms. Participants valued the opportunity to obtain both counseling and nicotine-replacement therapy products (intervention characteristics) and described forming a bond with the PTQ2 staff and reliance on them for emotional support and encouragement (characteristics of individuals). However, the culture of alcohol use and cigarette smoking around the shelter environment presented a serious challenge (outer setting). The study setting and the multiple competing needs of participants were reported as the most challenging barriers to implementation (implementation process). CONCLUSION: There are unique challenges in addressing smoking cessation with people experiencing homelessness. For those in shelters there can be the difficulty of pro-smoking norms in and around the shelter itself. Considering pairing cessation with policy level interventions targeting smoke-free spaces, or pairing cessation with housing support efforts may be worthwhile.. Participants described a discord in their personal goals of reduction compared with the study goals of complete abstinence, which may pose a challenge to the ways in which success is defined for people experiencing homelessness. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01932996 , registered 08/30/2013.

Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study.

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.

Psychosocial Well-Being and Progression of Coronary Artery Calcification in Midlife Women.

Background Prevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well-being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well-being was associated with less progression of coronary artery calcium (CAC). Methods and Results Participants were 312 women (mean age 50.8) from the SWAN (Study of Women's Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well-being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well-being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well-being was associated with less progression (RR, 0.909; 95% CI, 0.843-0.979; P=0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871-1.020; P=0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852-0.995; P=0.037). Conclusions Optimum early prevention of CVD in women may result from including the mind side of the mind-heart-body continuum.

Associations between a sense of connection and existential and psychosocial outcomes in gynecologic and breast cancer survivors.

BACKGROUND: A cancer diagnosis may lead to existential despair but potentially also to perceived inner growth. This growth may be fostered through meaningful connections with others. We sought to describe existential and related psychosocial outcomes and their association with a sense of connection with others in individuals with gynecological and breast cancers. METHODS: We used cross-sectional data from two ongoing cohort studies of gynecologic (N = 236) and breast (N = 62) cancer survivors at the University of Minnesota. We summarized self-reported post-traumatic growth (PTG), sense of meaning, peace, spirituality, hopelessness, loneliness, and three exploratory measures of sense of connections with others, and used multivariate linear regression models to describe the associations between them. RESULTS: Hope, sense of meaning, peace, and spirituality were generally high among participants, but PTG and loneliness scores varied more. Sense of connection with others was consistently associated with greater PTG and decreased loneliness with medium effect sizes: for example having positive interactions with most/all versus nobody on one's medical team, PTG (coefficient 10.49, 95% CI: 4.10, 16.87, Cohen's D 0.44); loneliness (coefficient - 0.85, 95% CI: - 1.36, - 0.34, Cohen's D 0.43). Those who knew someone in a similar life situation felt a strong sense of connection with such a person; however, 28% of participants had not met anyone in a similar situation. CONCLUSIONS: There may be untapped opportunities to nurture beneficial existential outcomes in cancer survivors. Potential interventions include connecting survivors with one another and creating opportunities for more authentic patient-provider relationships, for example, within palliative care.

Utility of Repeat Testing for Congenital Hypothyroidism in Infants with Very Low Birth Weight.

OBJECTIVE: To assess for possible missed hypothyroidism in infants of very low birth weight (VLBW) whose initial newborn screening (NBS) was within normal reference range. STUDY DESIGN: We analyzed serum thyroid-stimulating hormone (TSH) obtained at 36 weeks of corrected gestational age or at hospital discharge if earlier (retest TSH) in infants with VLBW in the neonatal intensive care unit to determine the prevalence and factors associated with retest TSH ≥5 mU/L, a concentration requiring close follow-up for hypothyroidism. Utility of alternative cut-offs for NBS TSH also was assessed. RESULTS: A total of 398 infants, median gestational age 29 (range 22-36) weeks, birth weight 1138 (470-1498) g, were included in this study. Retest TSH was obtained at 49.5 (12-137) days after birth. Median retest TSH was 3.1 (0.5-27.9) mU/L. Seventy-three (18.3%) of the cohort had retest TSH ≥5 mU/L. Adjusting NBS cut-off to ≥15 or ≥10 mU/L identified <50% of infants with TSH ≥5 mU/L, resulting in 6% false positives and >70% false negatives. Multiple regression modeling indicated that 35% of variance in retest TSH value was explained by NBS TSH concentration, birth weight, and gestational age, all P < .01. CONCLUSIONS: Retesting for hypothyroidism at 36 weeks of corrected gestational age in infants with VLBL and normal NBS could identify infants who require ongoing surveillance until thyroid function has been definitively ascertained. Adjusting NBS TSH cutoffs is not a valid option for identifying potential hypothyroidism in infants with VLBW because of lack of sensitivity and unacceptable false-positive and false-negative rates.

Comparing adolescent self staging of pubertal development with hormone biomarkers.

OBJECTIVES: Physical examinations to characterize pubertal maturation may be unacceptable for children enrolled in research studies. Studies confirm the utility of pubertal self staging for research, but there has been limited comparison of self examination with hormone biomarkers. Our objective was to assess concordance of pubertal self staging with hormone biomarkers of puberty. METHODS: Participants were enrolled in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort study. At age 12 years, 139 females and 112 males completed pubertal self staging including breast and pubic hair development in females and pubic hair development in males. No clinical physical examination was performed. Hormone concentrations were measured in 102 females and 96 males including serum dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in all; estradiol in females; and testosterone in males. RESULTS: Estradiol was significantly associated with female breast stage, even when adjusted for BMI, with geometric least squares means (95%CI) of 13.2 (8.7, 20.2), 38.3 (29.9, 49.1), 59.4 (39.8, 88.6), and 81.2 (45.6, 144) pg/mL for breast stage 1-2, 3, 4, and 5, respectively. Testosterone was significantly associated with male pubic hair stage, with adjusted geometric least squares means (95%CI) of 37.6 (19.9, 71.1), 43.4 (27.7, 68.3), 126 (78.4, 203), 275 (146, 521), and 559 (237, 1319) ng/dL for pubic hair stage 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: Self assessed pubertal development was positively associated with hormonal biomarkers of puberty.