Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer.

Most high-grade serous ovarian cancer (HGSOC) patients develop resistance to platinum-based chemotherapy and recur, but 15% remain disease free over a decade. To discover drivers of long-term survival, we quantitatively analyzed the proteomes of platinum-resistant and -sensitive HGSOC patients from minute amounts of formalin-fixed, paraffin-embedded tumors. This revealed cancer/testis antigen 45 (CT45) as an independent prognostic factor associated with a doubling of disease-free survival in advanced-stage HGSOC. Phospho- and interaction proteomics tied CT45 to DNA damage pathways through direct interaction with the PP4 phosphatase complex. In vitro, CT45 regulated PP4 activity, and its high expression led to increased DNA damage and platinum sensitivity. CT45-derived HLA class I peptides, identified by immunopeptidomics, activate patient-derived cytotoxic T cells and promote tumor cell killing. This study highlights the power of clinical cancer proteomics to identify targets for chemo- and immunotherapy and illuminate their biological roles.

Food insecurity and quality of life in patients with sickle cell disease.

Little is known about the relationship between quality of life (QOL) and food insecurity (FI) among patients with sickle cell disease (SCD). We hypothesized FI is associated with lower QOL in children and young adults with SCD. Overall (N = 99), 22% screened positive for FI. Supplemental Nutrition Assistance Program (SNAP) enrollment was 50 and 71% among people from food secure and FI households, respectively. A higher FI score was correlated with lower overall QOL (r = -0.22, p = .03), specifically lower QOL in worry and communication domains. Interventions for FI beyond SNAP may be important for QOL among people living with SCD.

Collaborative Integration of Community Health Workers in Hospitals and Health Centers to Reduce Pediatric Asthma Disparities: A Quality Improvement Program Evaluation.

To address pediatric asthma disparities on the South Side of Chicago, a community health worker (CHW) home visiting intervention was implemented collaboratively by academic institutions and community based health centers. This evaluation assessed the effectiveness of this longitudinal quality improvement CHW intervention in reducing asthma morbidity and healthcare utilization. All patients aged 2-18 who met the high-risk clinical criteria in outpatient settings or those who visited the ED due to asthma were offered the program. A within-subject study design analyzed asthma morbidity and healthcare utilization at baseline and follow-up. Multivariable mixed-effects regression models, adjusted for baseline demographic and asthma characteristics, were used to assess changes over time. Among 123 patients, the average age was 8.8 (4.4) years, and 89.3% were non-Hispanic black. Significant reductions were observed in the average daytime symptoms days (baseline 4.1 days and follow-up 1.6 days), night-time symptoms days (3.0 days and 1.2 days), and days requiring rescue medication (4.1 days and 1.6 days) in the past two weeks (all p < 0.001). The average number of emergency department visits decreased from 0.92 one year before to 0.44 one year after program participation, a 52% reduction (p < 0.001). No significant difference was found in hospital admissions. These results support the use of a collaborative approach to implement the CHW home visiting program as part of standard care for pediatric asthma patients in urban settings. This approach has the potential to reduce asthma disparities and underscores the valuable role of CHWs within the clinical care team.

Unwanted sexual activity among United States women early in the COVID-19 pandemic.

BACKGROUND: Female sexual activity and, accordingly, birth rates tend to decline in times of stress, such as a pandemic. In addition, when resources are scarce or exogenous conditions are threatening, some women may engage in sexual activity primarily to maintain socioeconomic security. Having unwanted sex may indicate sexual activity in exchange for economic security. OBJECTIVE: This study aimed to describe patterns and correlates of unwanted sex, defined as having sex more frequently than desired, among US women early in the COVID-19 pandemic. STUDY DESIGN: The National US Women's Health COVID-19 Study was conducted in April 2020, using a nested quota sample design to enroll 3200 English-speaking women (88% cooperation rate) aged 18 to 90 years recruited from a research panel. The quota strata ensured sufficient sample sizes in sociodemographic groups of interest, namely, racial and ethnic subgroups. Patterns of sexual activity, including unwanted sex early in the pandemic, were described. To further elucidate the experiences of women reporting unwanted sex, open-ended responses to an item querying "how the coronavirus pandemic is affecting your sex life" were assessed using conventional content analysis. Logistic regression analyses-adjusting for sociodemographic characteristics, self-reported health, and prepandemic health-related socioeconomic risk factors, including food insecurity, housing instability, utilities and transportation difficulties, and interpersonal violence-were used to model the odds of unwanted sex by a pandemic-related change in health-related socioeconomic risk factors. RESULTS: The proportion of women who were sexually active early in the pandemic (51%) was about the same as in the 12 months before the pandemic (52%), although 7% of women became active, and 7% of women became inactive. Overall, 11% of sexually active women were having unwanted sex in the early pandemic. The rates of anxiety, depression, traumatic stress symptoms, and each of the 5 health-related socioeconomic risk factors assessed were about 2 times higher among women having unwanted sex than other women (P<.001). Women having unwanted sex were also 5 times more likely than other women to report an increased frequency of sex since the pandemic (65% vs 13%; P<.001) and 6 times more likely to be using emergency contraception (18% vs 3%; P<.001). Women reporting unwanted sex commonly described decreased libido or interest in sex related to mood changes since the pandemic, having "more sex," fear or worry about the transmission of the virus because of sex, and having sex to meet the partner's needs. Among sexually active women, the odds of unwanted sex (adjusting for demographic, reproductive, and health factors) were higher among women with 1 prepandemic health-related socioeconomic risk factor (adjusted odds ratio, 2.0; 95% confidence interval, 1.1-3.8) and 2 or more prepandemic health-related socioeconomic risk factors (adjusted odds ratio, 6.0; 95% confidence interval, 3.4-10.6). Among sexually active women with any prepandemic health-related socioeconomic risk factor, those with new or worsening transportation difficulties early in the pandemic were particularly vulnerable to unwanted sex (adjusted odds ratio, 2.7; 95% confidence interval, 1.7-4.3). CONCLUSION: More than 1 in 10 sexually active US women was having unwanted sex early in the COVID-19 pandemic. Socioeconomically vulnerable women, especially those with new or worsening transportation problems because of the pandemic, were more likely than others to engage in unwanted sex. Pandemic response and recovery efforts should seek to mitigate unwanted sexual activity and related health and social risks among women.

Breast sensorisexual function: a novel patient-reported outcome measure of sexual sensory functions of the breast.

BACKGROUND: A validated measure assessing sexual sensory functions of the breast is needed to optimize sexual and other health outcomes after breast procedures. AIM: To describe the development of a patient-reported outcome measure (PROM) to assess breast sensorisexual function (BSF). METHODS: We applied the PROMIS standards (Patient Reported Outcomes Measurement Information System) for measure development and evaluation of validity. An initial conceptual model of BSF was developed with patients and experts. A literature review yielded a pool of 117 candidate items that underwent cognitive testing and iteration. Forty-eight items were administered to an ethnically diverse, national panel-based sample of sexually active women with breast cancer (n = 350) or without (n = 300). Psychometric analyses were performed. OUTCOMES: The main outcome was BSF, a measure that assesses affective (satisfaction, pleasure, importance, pain, discomfort) and functional (touch, pressure, thermoreception, nipple erection) sensorisexual domains. RESULTS: A bifactor model fit to 6 domains-excluding 2 domains with only 2 items each and 2 pain-related domains-revealed a single general factor representing BSF that may be adequately measured by the average of the items. This factor, with higher values denoting better function and with the standard deviation set to 1, was highest among women without breast cancer (mean, 0.24), intermediate among women with breast cancer but not bilateral mastectomy and reconstruction (-0.01), and lowest among those with bilateral mastectomy and reconstruction (-0.56). Between women with and without breast cancer, the BSF general factor accounted for 40%, 49%, and 100% of the difference in arousal, ability to orgasm, and sexual satisfaction, respectively. Items in each of 8 domains demonstrated unidimensionality (ie, they measured 1 underlying BSF trait) and high Cronbach's alphas for the entire sample (0.77-0.93) and the cancer group (0.71-0.95). Correlations with sexual function, health, and quality of life were positive for the BSF general factor and mostly negative for the pain domains. CLINICAL IMPLICATIONS: The BSF PROM can be used to assess the impact of breast surgery or other procedures on the sexual sensory functions of the breast in women with and without breast cancer. STRENGTHS AND LIMITATIONS: The BSF PROM was developed by using evidence-based standards, and it applies to sexually active women with and without breast cancer. Generalizability to sexually inactive women and other women warrants further study. CONCLUSION: The BSF PROM is a measure of women's breast sensorisexual function with evidence of validity among women affected and unaffected by breast cancer.

Assessing how Age, Sex, Race, and Education Affect the Relationships Between Cognitive Domains and Odor Identification.

BACKGROUND: The associations between cognitive domains and odor identification are well established, but how sociodemographic variables affect these relationships is less clear. PURPOSE: Using the survey-adapted Montreal Cognitive Assessment instrument (MoCA-SA), we assess how age, sex, race, and education shape these relationships. METHODS: We first used cluster analysis and multidimensional scaling to empirically derive distinct cognitive domains from the MoCA-SA as it is unclear whether the MoCA-SA can be disaggregated into cognitive domains. We then used ordinal logistic regression to test whether these empirically derived cognitive domains were associated with odor identification and how sociodemographic variables modified these relationships. STUDY POPULATION: Nationally representative sample of community-dwelling US older adults. RESULTS: We identified 5 out of the 6 theoretical cognitive domains, with the language domain unable to be identified. Odor identification was associated with episodic memory, visuospatial ability, and executive function. Stratified analyses by sociodemographic variables reveal that the associations between some of the cognitive domains and odor identification varied by age, sex, or race, but not by education. CONCLUSIONS: These results suggest that (1) the MoCA-SA can be used to identify cognitive domains in survey research and (2) the performance of smell tests as a screener for cognitive decline may potentially be weaker in certain subpopulations.

Growth After Menarche in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Growth impairment in pediatric patients with pediatric onset inflammatory bowel disease (IBD) is multifactorial. Reports on the effect of age at menarche on adult stature in this population are limited. This study investigated the impact of age at menarche, disease-associated factors, and mid-parental height on growth from menarche to final height (FHt) in pediatric patients with Crohn disease (CD) and ulcerative colitis (UC) and IBD unclassified (IBD-U). METHODS: Subjects were enrolled from a prospectively maintained pediatric IBD database when IBD preceded menarche and dates of menarche and FHt measurements were recorded. RESULTS: One hundred forty-six patients: CD 112 and UC 30/IBD-U 4. Mean age (years) at diagnosis (10.9 vs 10.1), menarche (14.4 vs 14.0), and FHt (19.6 vs 19.7). CD and UC/IBD-U patients showed significant association between Chronological age (CA) at menarche and FHt (cm, P < 0.001) but not FHt z score (FHt-Z) < -1.0 (P = 0.42). FHt-Z < -2.0 occurred in only 5 patients. Growth impairment (FHt-Z < -1.0) was associated with surgery before menarche (P = 0.03), jejunal disease (P = 0.003), low mid-parental height z score (MPH-Z) (P < 0.001), hospitalization for CD (P = 0.03) but not UC, recurrent corticosteroid, or anti-tumor necrosis factor alpha (anti-TNFα) therapy. CONCLUSIONS: Early age of menarche was associated with greater potential for linear growth to FHt but not FHt-Z (P < 0.05). Surgery before menarche, jejunal disease, hospitalization for CD, low MPH, and weight z score were associated with FHt-Z < -1.0.

Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions.

INTRODUCTION: Longitudinal multivariable analyses are needed to determine if the rate of olfactory decline during normal cognition predicts subsequent Alzheimer's disease (AD) diagnoses and brain dysmorphology. METHODS: Older adults (n = 515) were assessed annually for odor identification, cognitive function and dementia clinical diagnosis (max follow-up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross-sectional subsample (n = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors and demographics. RESULTS: Faster olfactory decline during periods of normal cognition predicted higher incidence of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, p < 0.01; comparable to carrying an APOE-ε4 allele) and smaller GMV in AD and olfactory regions (ß = -0.11, 95% CI -0.21, -0.00). DISCUSSION: Rapid olfactory decline during normal cognition, using repeated olfactory measurement, predicted subsequent cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early AD detection. HIGHLIGHTS: Rate of olfactory decline was calculated from olfactory testing over ≥3 time points. Rapid olfactory decline predicted impaired cognition and higher risk of dementia. Neurodegeneration on 3T magnetic resonance imaging was identical in those with olfactory decline and Alzheimer's disease.

The Effect of Body Mass Index and Weight-Adjusted Fluid Dosing on Mortality in Sepsis.

PURPOSE: The Surviving Sepsis Campaign guidelines recommend 30 mL/kg of fluids within 3 hours (30by3) of sepsis-induced hypoperfusion, but a national mandate released an allowance for dosing based on ideal instead of actual body weight (IBW/ABW) for obese patients. This study aims to determine the dose-effect of 30by3 for patients with severe sepsis or septic shock (SS/SS) with respect to body mass index (BMI) categories and secondarily, examine the clinical impact of IBW vs. ABW-based dosing. METHODS: Retrospective cohort study of adults (≥18 years; n = 1,032) with SS/SS presenting to an urban, tertiary-care emergency department. Models include MEDS score, antibiotic timing, lactate, renal and heart failure, among others. RESULTS: The cohort was 10.2% underweight and 28.7% obese. Overall mortality was 17.1% with 20.4% shock mortality. An exponential increase in mortality was observed for each 5 mL/kg under 30by3 for underweight (p = 0.02), but not obese patients. ABW vs IBW-30by3 dosing was reached in 80.0 vs 52.4% (underweight), 56.4 vs 56.9% (normal/overweight), and 23.3 vs 46.0% (obese). Across all BMI categories, there was increased mortality for not reaching ABW-based 30by3 dosing (OR 1.78, 95% CI 1.18-2.69) with no significant impact for IBW (OR 1.28, 95% CI 0.87 -1.91). The increased mortality for failing to reach ABW-dosed 30by3 remained for underweight patients ABW (OR 5.82, 95% CI 1.32-25.57) but not obese patients. Longer ICU stays were observed for not reaching 30by3 based on ABW (ß = 2.40, 95% CI 0.84-3.95) and IBW dosing (ß = 1.58, 95% CI 0.07-3.08) overall. This effect remained for obese and underweight (except IBW dosing) patients. CONCLUSIONS: An exponential, dose-effect increase in mortality was observed for underweight patients not receiving 30by3. Therefore, the mortality impact of under-dosing may be amplified using ABW for underweight patients. Fluid dosing did not impact mortality for obese patients, but we caution against deviation from guidelines without further studies.

Resilience: a mediator of the negative effects of pandemic-related stress on women's mental health in the USA.

The role of resilience in mediating the negative effects of the COVID-19 pandemic on the mental health of US women is poorly understood. We examined socioeconomic factors associated with low resilience in women, the relationship of low resilience with psychiatric morbidity, and the mediating role of resilience in the relationship between pandemic-related stress and other coincident psychiatric morbidities. Using a quota-based sample from a national panel, we conducted a web-based survey of 3200 US women in April 2020. Weighted, multivariate logistic regression was used to model the odds of pandemic-related stress, and coincident depression and anxiety symptoms among those with and without low resilience. Structural equation modeling was used to evaluate resilience as a mediator of the relationship between pandemic-related stress and other coincident psychiatric morbidities. Risk factors for low resilience included younger age, lower household income, lower education, unemployment, East/Southeast Asian race, unmarried/unpartnered status, and higher number of medical comorbidities. Low resilience was significantly associated with greater odds of depression symptoms (OR = 3.78, 95% CI [3.10-4.60]), anxiety symptoms (OR = 4.17, 95% CI [3.40-5.11]), and pandemic-related stress (OR = 2.86, 95% CI [2.26-3.26]). Resilience acted as a partial mediator in the association between pandemic-related stress and anxiety symptoms (proportion mediated = 0.23) and depression symptoms (proportion mediated = 0.28). In the early days of the COVID-19 pandemic, low resilience mediated the association between pandemic-related stress and psychiatric morbidity. Strategies proven to enhance resilience, such as cognitive behavioral therapy, mindfulness-based stress reduction, and addressing socioeconomic factors, may help mitigate mental health outcomes.

Exploring Shared Effects of Multisensory Impairment, Physical Dysfunction, and Cognitive Impairment on Physical Activity: An Observational Study in a National Sample.

Multisensory, physical, and cognitive dysfunction share age-related physiologic disturbances and may have common health effects. We determined whether the effect of multisensory impairment on physical activity (PA) is explained by physical (timed up and go) or cognitive (Short Portable Mental Status Questionnaire) dysfunction. A National Social Life, Health, and Aging Project participant subset (n = 507) underwent objective sensory testing in 2005-2006 and wrist accelerometry in 2010-2011. We related multisensory impairment to PA using multivariate mixed-effects linear regression and compared the effect magnitude after adjusting for physical then cognitive dysfunction. Worse multisensory impairment predicted lower PA across three scales (Global Sensory Impairment: ß = -0.04, 95% confidence interval [-0.07, -0.02]; Total Sensory Burden: ß = -0.01, 95% confidence interval [-0.03, -0.003]; and Number of Impaired Senses: ß = -0.02, 95% confidence interval [-0.04, -0.004]). Effects were similar after accounting for physical and cognitive dysfunction. Findings suggest that sensory, physical, and cognitive dysfunction have unique mechanisms underlying their PA effects.

Sleep quality and glycaemic variability in a real-life setting in adults with type 1 diabetes.

AIMS/HYPOTHESIS: Suboptimal subjective sleep quality is very common in adults with type 1 diabetes. Reducing glycaemic variability is a key objective in this population. To date, no prior studies have examined the associations between objectively measured sleep quality and overnight glycaemic variability in adults with type 1 diabetes. We aimed to test the hypothesis that poor sleep quality would be associated with greater overnight glycaemic variability. METHODS: Data were collected in the home setting from 20 adults (ten male and ten female participants) with type 1 diabetes who were current insulin pump users. Simultaneous assessments of objective sleep quality (Zmachine Insight+) and continuous glucose monitoring (CGM) were performed over multiple nights (up to 15 nights) in each participant. Due to the real-life nature of this study, the participants kept their usual CGM alerts for out-of-range glucose values. Sleep quality was categorised as 'good' or 'poor' using a composite of objective sleep features (i.e. sleep efficiency, wake after sleep onset and number of awakenings) based on the National Sleep Foundation's consensus criteria. Glycaemic variability was quantified using SD and CV of overnight glucose values based on overnight CGM profiles. RESULTS: A total of 170 nights were analysed. Overall, 86 (51%) nights were categorised as good sleep quality, and 84 (49%) nights were categorised as poor sleep quality. Using linear mixed-effects models, poor sleep quality was significantly associated with greater glycaemic variability as quantified by SD (coefficient: 0.39 [95% CI 0.10, 0.67], p = 0.009) and CV (coefficient: 4.35 [95% CI 0.8, 7.9], p = 0.02) of overnight glucose values, after accounting for age, sex, BMI and overnight insulin dose. There was large inter- and intra-individual variability in sleep and glycaemic characteristics. Both pooled and individual-level data revealed that the nights with poor sleep quality had larger SDs and CVs, and, conversely, the nights with good sleep quality had smaller SDs and CVs. No associations were found between sleep quality and time spent in the target glucose range, or above or below the target glucose range, where CGM alarms are most likely to occur. CONCLUSIONS/INTERPRETATION: Objectively measured sleep quality is associated with overnight glycaemic variability in adults with type 1 diabetes. These findings highlight an important role of sleep quality in overnight glycaemic control in type 1 diabetes. They also provide a strong incentive to both patients and healthcare providers for considering sleep quality in personalised type 1 diabetes glycaemic management plans. Future studies should investigate the mechanisms linking sleep quality to glycaemic variability.

Patient Perceptions Impact Progression to Third-Line Therapy for Treatment of Overactive Bladder.

PURPOSE: We aimed to understand the reasons patients choose to pursue third-line overactive bladder (OAB) therapy. MATERIALS AND METHODS: We conducted a mixed methods study that included patient interviews and survey data. Eligible patients were diagnosed by symptoms, had tried behavioral modifications, and OAB medications enrolled from October 2018 to August 2019. In addition to interviews, patients completed 4 surveys: the Pelvic Floor Distress Inventory, Overactive Bladder Questionnaire Short Form, Life Orientation Test-Revised, and a patient confidence in the health care system survey. Qualitative interview data were analyzed thematically. Logistic regression and chi-square analysis was used to analyze survey data. RESULTS: A total of 69 patients were consented, 4 withdrew, and 51 completed both interview and survey data. Overall 55% of patients were Caucasian, 45% were African American, and their average age was 71 (SD=10.4); 75% intended to pursue third-line OAB therapy and 31 (61%) expressed interest in a specific third-line therapy. Major interview themes included a desire for a better quality of life, embarrassment with accidents, and problems with medication. Themes leading patients away from third-line OAB treatment included concern about invasiveness and side effects of treatments, and restrictions to accessing care. CONCLUSIONS: Most patients desired to progress to third-line OAB therapy, were motivated by embarrassment, but were concerned about treatment side effects. We found that economic burden of OAB treatment is associated with patient interest in and decision to receive third-line therapies to include onabotulinumtoxinA and percutaneous tibial nerve stimulation. Improved quality of life, medication frustration, and concerns about side effects of further therapy are themes patients identified when patients considered third-line overactive bladder therapy.

Olfactory Dysfunction Predicts the Development of Depression in Older US Adults.

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00-1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13-4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression.

Intrathecal Morphine for Analgesia in Minimally Invasive Cardiac Surgery: A Randomized, Placebo-controlled, Double-blinded Clinical Trial.

BACKGROUND: Intrathecal morphine decreases postoperative pain in standard cardiac surgery. Its safety and effectiveness have not been adequately evaluated in minimally invasive cardiac surgery. The authors hypothesized that intrathecal morphine would decrease postoperative morphine consumption after minimally invasive cardiac surgery. METHODS: In this randomized, placebo-controlled, double-blinded clinical trial, patients undergoing robotic totally endoscopic coronary artery bypass received either intrathecal morphine (5 mcg/kg) or intrathecal saline before surgery. The primary outcome was postoperative morphine equivalent consumption in the first 24 h after surgery; secondary outcomes included pain scores, side effects, and patient satisfaction. Pain was assessed via visual analog scale at 1, 2, 6, 12, 24, and 48 h after intensive care unit arrival. Opioid-related side effects (nausea/vomiting, pruritus, urinary retention, respiratory depression) were assessed daily. Patient satisfaction was evaluated with the Revised American Pain Society Outcome Questionnaire. RESULTS: Seventy-nine patients were randomized to receive intrathecal morphine (n = 37) or intrathecal placebo (n = 42), with 70 analyzed (morphine 33, placebo 37). Intrathecal morphine patients required significantly less median (25th to 75th percentile) morphine equivalents compared to placebo during first postoperative 24 h (28 [16 to 46] mg vs. 59 [41 to 79] mg; difference, -28 [95% CI, -40 to -18]; P < 0.001) and second postoperative 24 h (0 [0 to 2] mg vs. 5 [0 to 6] mg; difference, -3.3 [95% CI, -5 to 0]; P < 0.001), exhibited significantly lower visual analog scale pain scores at rest and cough at all postoperative timepoints (overall treatment effect, -4.1 [95% CI, -4.9 to -3.3] and -4.7 [95% CI, -5.5 to -3.9], respectively; P < 0.001), and percent time in severe pain (10 [0 to 40] vs. 40 [20 to 70]; P = 0.003) during the postoperative period. Mild nausea was more common in the intrathecal morphine group (36% vs. 8%; P = 0.004). CONCLUSIONS: When given before induction of anesthesia for totally endoscopic coronary artery bypass, intrathecal morphine decreases use of postoperative opioids and produces significant postoperative analgesia for 48 h.

Validity of The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS): a daily activity criterion checklist for infants and toddlers.

BACKGROUND: The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) is a 50-item, criterion-specified questionnaire that assesses a child's adaptive skills in everyday context and can be used in high-risk follow-up settings to identify risk for adverse neurodevelopmental outcome. Our aim was to validate the WIDEA-FS by comparing a sample of typically developing children to children with special health needs and to compare results to the Capute Scales, which include domains of including both the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). METHODS: Six hundred and sixty children (typically developing and having special healthcare needs) aged 0-36 months completed the WIDEA-FS, the CAT, and the CLAMS assessments. RESULTS: Children with special health needs scored significantly lower on the WIDEA than those with typical development. WIDEA-FS subscales were significantly associated with the CAT (WIDEA-FS self-care 0.87, social cognition 0.89) and the CLAMS (WIDEA-FS communication 0.96, social cognition 0.92) tests. CONCLUSIONS: The WIDEA-FS has concurrent validity with the CAT and CLAMS and construct validity in that children with special health needs have significantly poorer performance on the WIDEA-FS than children with typical development. IMPACT: The WIDEA-FS demonstrated both construct validity and concurrent validity with the Capute Scales, including the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). This is the first study to validate the use of the WIDEA-FS in children with typical development and children with special healthcare needs. The WIDEA-FS is a quick and valid checklist that can be used to assess neurodevelopmental functioning during daily activities in typically developing children and those at risk for neurodevelopmental differences.

Olfaction Is Associated With Sexual Motivation and Satisfaction in Older Men and Women.

BACKGROUND: Sensory function declines with age and may impact sexual function in older adults. Indeed, the sense of smell plays a uniquely strong role in sexual motivation. Therefore, olfactory dysfunction in older adults may be intimately linked to changes in sexual desire and satisfaction. AIM: To test whether impaired olfactory function is associated with decreased sexual activity and motivation in older adults. METHODS: Cross-sectional analysis of a nationally representative sample of community-dwelling older U.S. adults from the National Social Life, Health, and Aging Project. OUTCOMES: 2 modalities of olfactory function were measured (sensitivity to n-butanol and odor identification) via validated methods (Sniffin' Sticks). Respondents answered survey questions about frequency of sexual thoughts (motivation) and sexual activity, and satisfaction with their most recent sexual relationship. A wide range of demographic, health, and social information were also collected. RESULTS: Decreased olfactory function in older U.S. adults was associated with decreased sexual motivation (odds ratio 0.93, P = .03) and less emotional satisfaction with sex (odds ratio 0.89, P = .04), but not decreased frequency of sexual activity or physical pleasure, in analyses that were adjusted for age, gender, race, education, cognition, comorbidities, and depression. CLINICAL IMPLICATIONS: Olfactory dysfunction may affect sexuality in older adults. Potentially treatable causes of sensory loss should be addressed by clinicians to improve quality of life. STRENGTHS & LIMITATIONS: These results rely on validated olfactory testing, detailed measures of sexual attitudes and behaviors, and extensive demographic, health, and social history in a nationally representative sample of older U.S. adults. Owing to the cross-sectional nature of these analyses, we cannot determine causality. CONCLUSIONS: Olfactory dysfunction in older U.S. adults is associated with decreased sexual motivation and emotional satisfaction, potentially due to evolutionarily-conserved neurological links between olfaction and sexuality. Siegel JK, Kung SY, Wroblewski KE, et al. Olfaction Is Associated With Sexual Motivation and Satisfaction in Older Men and Women. J Sex Med 2021;18:295-302.

Factors Affecting Selenium Status in Infants on Parenteral Nutrition Therapy.

INTRODUCTION: Selenium is an essential micronutrient that must be supplemented in infants and young children on exclusive parenteral nutrition (PN). We examined selenium status and clinical factors associated with a deficiency in infants on PN. METHODS: This was a retrospective cohort study of pediatric patients receiving PN with routine monitoring of selenium status. Deficiency was diagnosed using age-based norms of plasma selenium status. Associations between selenium deficiency and the following clinical factors were examined: birthweight status: extremely low birthweight (ELBW) versus very low birthweight (VLBW) versus low birthweight (LBW) versus normal birthweight (NBW), serum albumin status, presence of cholestasis, and co-administration of enteral feeds. RESULTS: A total of 42 infants were included with gestational age [median (interquartile range)] 28 weeks (25,34). The prevalence of selenium deficiency was 80% and the prevalence of albumin deficiency was 87.5%. The odds of selenium deficiency were higher in ELBW infants (odds ratio = 17.84, 95% confidence interval [4.04-78.72], P < 0.001) and VLBW infants (odds ratio = 16.26, 95% confidence interval [1.96-135.04], P < 0.001) compared to NBW infants. The odds of selenium deficiency were 5-fold higher in patients with low serum albumin (odds ratio = 5.33, 95% confidence interval [1.39-20.42], P = 0.015). There were no associations seen between selenium status and presence of cholestasis or co-administration of enteral feeds. CONCLUSION: In this cohort of infants on PN therapy, the main clinical factors associated with selenium deficiency were presence of hypoalbuminemia and history of ELBW or VLBW. These findings support dual measurement of serum albumin and serum selenium to improve interpretation of selenium status.

Concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills and the Bayley Scales of Infant and Toddler Development, Third Edition.

AIM: To determine the concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS), a criterion-specified questionnaire that assesses a child's adaptive skills in everyday contexts, and the Bayley Infant and Toddler Scales of Development, Third Edition (Bayley-III). METHOD: In a prospective cohort study, 431 WIDEA-FS and Bayley-III assessments were completed among 341 children, aged 10 to 36 months corrected age (158 females, 183 males; median [interquartile range] gestational age at birth 32wks [29-38]), monitored in a high-risk neonatal intensive care unit follow-up clinic. RESULTS: WIDEA-FS scores were significantly associated with Bayley-III scores in all domains. Lower scores on the WIDEA-FS were significantly associated with an increased risk of adverse developmental performance on all Bayley-III scales. The association was strongest for motor and language Bayley-III scores when tested at <30 months of age, and for cognitive Bayley-III scores when tested at ≥30 months of age. INTERPRETATION: The WIDEA-FS has concurrent validity with the Bayley-III and may be a useful tool in high-risk follow-up settings. WHAT THIS PAPER ADDS: WIDEA-FS mobility, communication, and social cognition domains are concurrently valid in infants at high-risk for neurodevelopmental disability. Bayley-III motor, language, and cognitive composite scores are concurrently valid in the same group. The WIDEA-FS mobility and communication domains may be most clinically useful in children <30 months.

Physician and Nurse Practitioner Attitudes on Generic Prescribing of Oral Contraceptive Pills and Antidepressants.

IMPORTANCE: As prescription drug costs rise, it is important to understand attitudes among primary care physicians and nurse practitioners (NPs) towards generic drugs. OBJECTIVE: We aimed to examine the generic skepticism index (GSI) among primary care clinicians, and their willingness to discuss and prescribe generic antidepressants (ADs) and generic oral contraceptives (OCPs). DESIGN: We used a factorial vignette design survey to test 4 factors: message source, message, brand preference, and drug class. Participants were randomized to different combinations of factors. SETTING: This was a cross-sectional study. PARTICIPANTS: Physicians registered with the American College of Physicians (ACP) and NPs registered with the American Association of Nurse Practitioners (AANP) participated in the study. MAIN MEASURES: The primary outcomes were generic skepticism as measured using the generic skepticism index (GSI), and clinician willingness to discuss and prescribe generics. RESULTS: Surveys were completed by 56% of physicians (n = 369/661) and 60% of NPs (n = 493/819). Compared with physicians, NPs were younger (p < 0.001), predominantly female (p < 0.001), and differed in the race (p < 0.001). According to the GSI, 16% (n = 138/862) were identified as generic skeptics (18.5% of NPs and 12.7% of physicians, p = 0.023). Generic skeptics had lower odds of willingness to discuss switching (OR 0.22, 95% CI (0.14-0.35), p < 0.001) or prescribe (OR 0.18, 95% CI (0.11-0.28), p < 0.001) generic OCPs. Participants had lower odds of willingness to prescribe generic drugs to patients with brand preference compared with brand-neutral patients (OR 0.64, 95% CI 0.50-0.82, p < 0.001). CONCLUSIONS AND RELEVANCE: Generic skepticism was associated with lower willingness to discuss or prescribe generic drugs. Clinicians reported lower willingness to discuss switching or prescribe generics for OCPs than for ADs. Patient brand preference hindered generic prescribing. Message source and message type were not significantly associated with outcomes.