Clinical impact of less invasive surfactant administration using video laryngoscopy in extremely preterm infants.

BACKGROUND: Examine the real-world clinical impact of adopting less invasive surfactant administration (LISA) as the primary surfactant administration method in extremely preterm infants. METHODS: Single-center pre-post cohort study conducted over a 4-year period comparing outcomes of spontaneously breathing inborn infants 24+0-28+6 weeks gestational age (GA) receiving surfactant via endotracheal tube (pre-cohort, n = 154) or LISA via thin catheter (post-cohort, n = 70). Primary outcome was need for invasive mechanical ventilation (IMV, ≥2 h) ≤72 h of age. Secondary outcomes were a composite of mortality, bronchopulmonary dysplasia, intraventricular hemorrhage ≥grade 3 or necrotizing enterocolitis, and its individual components. Groups were compared using propensity score methods, including covariates: GA, birth weight, sex, small for GA, SNAP II ≥20, premature rupture of membranes, maternal hypertension/diabetes, and C-section. RESULTS: GA and birth weight were 27.1 (26, 28.1) weeks and 914 (230) g, and 27.1 (26.1, 28.1) weeks and 920 (236) g for pre- and post-cohorts, respectively. Pre-cohort had higher C-section rates, (67% vs. 51%, p = 0.03). After adjustment for covariates, LISA was associated with reduced IMV exposure [AOR (95% CI) 0.07 (0.04, 0.11)], lower odds of the composite clinical outcome [0.49 (0.33, 0.73)], and most of its individual components. CONCLUSION: Real-world experience favors LISA as the primary method in extremely preterm infants with established spontaneous respiration. IMPACT: Less invasive surfactant administration (LISA) is associated with a reduction in respiratory morbidity, but real-world data of routine use among extremely preterm infants are limited. LISA is associated with reduced frequency of exposure to and duration of IMV in both ≤72 h after birth and during hospital stay. LISA is associated with a reduction in mortality, and most other major morbidities including bronchopulmonary dysplasia, and interventricular hemorrhage. Data from a large North American center providing real-world clinical outcomes following LISA as the primary method of surfactant administration.

Anxiety and Anticipated Pain Levels of Women With Self-Reported Penetration-Related Genito-Pelvic Pain are Elevated in Response to Pain-related Images.

BACKGROUND: Genito-pelvic pain (GPP) affects a sizable minority of women and results of existing treatments can be variable. A method of general pain treatment that has not yet been extended to penetration-related GPP is Explicit Motor Imagery (EMI), which uses pain-related images to help individuals with pain alter their responses to pain, resulting in reduced pain, less pain-related anxiety, and improved function. AIM: As a first step toward determining if EMI is a feasible method for treating penetration-related GPP, this study examined whether images that potentially signal genital pain are sufficient to induce an anxiety or anticipated pain response in women. METHODS: Participants were 113 women (62 with genital pain, 51 pain-free) recruited to complete an online study. Participants viewed randomized images of women engaging in various activities that potentially cause pain for people with penetration-related GPP (sitting, walking, running, lifting, inserting a tampon, implied penetrative sex, actual penetrative sex, implied gynecological exam, actual gynecological exam). Participants then rated each image on how much anxiety they experienced viewing the picture (viewing anxiety), and how much anxiety (anticipated anxiety) and pain (anticipated pain) they expected to experience doing the activity in the picture. OUTCOMES: Outcomes were the self-reported viewing anxiety, anticipated anxiety, and anticipated pain of women with and without self-reported penetration-related GPP in response to the pain-related images. RESULTS: Women who experienced self-reported penetration-related GPP reported significantly higher levels of viewing anxiety, anticipated anxiety, and anticipated pain in almost all categories of images, compared to women who were free of pain. The key exception was that women with and without self-reported penetration-related GPP reported similar levels of viewing anxiety when looking at images of implied and actual penetrative sex. CLINICAL TRANSLATION: These results support that pelvic and genital imagery serve as a sufficient stimulus to generate anxiety and anticipated pain in our study sample. EMI, which targets desensitization of heightened anxiety warrants further research as a potential novel treatment option. STRENGTHS & LIMITATIONS: This study was the first to assess responses to a wide array of pain-eliciting images in women with and without self-reported penetration-related GPP. A key limitation was that the pain sample was self-reported and not clinically diagnosed. CONCLUSION: Images of pain-related stimuli were sufficient to induce anxiety and anticipated pain in women with self-reported penetration-related GPP. This first step suggests that EMI may be a useful treatment option for women with penetration-related GPP. Kelly KJM, Fisher BL, Rosen NO, et al. Anxiety and Anticipated Pain Levels of Women With Self-Reported Penetration-Related Genito-Pelvic Pain are Elevated in Response to Pain-related Images. J Sex Med 2022;19:1281-1289.

Management of biogenic taste and odour: From source water, through treatment processes and distribution systems, to consumers.

Biogenic taste and odour (T&O) have become a global concern for water utilities, due to the increasing frequency of algal blooms and other microbial events arising from the combined effects of climate change and eutrophication. Microbially-produced T&O compounds impact source waters, drinking water treatment plants, and drinking water distribution systems. It is important to manage across the entire biogenic T&O pathway to identify key risk factors and devise strategies that will safeguard the quality of drinking water in a changing world, since the presence of T&O impacts consumer confidence in drinking water safety. This study provides a critical review of current knowledge on T&O-causing microbes and compounds for proactive management, including the identification of abiotic risk factors in source waters, a discussion on the effectiveness of existing T&O barriers in drinking water treatment plants, an analysis of risk factors for biofilm growth in water distribution systems, and an assessment of the impacts of T&O on consumers. The fate of biogenic T&O in drinking water systems is tracked from microbial production pathways, through the release of intracellular T&O by cell lysis, to the treatment of microbial cells and dissolved T&O. Based on current knowledge, five impactful research and management directions across the T&O pathway are recommended.

Reduced No-Show Rates and Sustained Patient Satisfaction of Telehealth During the COVID-19 Pandemic.

Introduction: The unprecedented COVID-19 pandemic has thrust telehealth into the center stage of health care, leading to a dramatic increase in utilization of telehealth services. The impact of telehealth on patient satisfaction during the current pandemic is yet to be fully understood. Objective: This study aimed to identify patient perspectives and behaviors toward virtual primary care appointments at a telehealth-naïve institution during the COVID-19 pandemic and establish the rate of missed appointments to help guide future implementation of telehealth services. Methods: Patients at a primary and specialty care clinic, seen between March and May 2020, completed a survey analyzing nine commonly used satisfaction metrics. The rate of missed appointments was recorded and compared with analogous cohorts of in-person office visits. Results: The no-show rate of telehealth visits during the COVID-19 pandemic was 7.5% (14/186), lower than both the no-show rate of 36.1% for in-office visits (56/155) (p < 0.0001) and a pre-pandemic in-office no-show rate of 29.8% (129/433) (p < 0.0001). Surveyed patients who experienced telehealth visits (n = 65) had similar satisfaction compared with those surveyed who attended in-office visits (n = 36) in seven of nine metrics. No statistically significant differences were identified in the satisfaction metrics with telehealth visits performed on video (n = 26) versus the phone-only format (n = 38). Patients aged 65 years or over were less likely to have a video component to their virtual visit (1/12, 8.3%) than those under age 65 (25/44, 56.8%) (p = 0.0031). Discussion/Conclusions: Telehealth offers significant benefits for both patients and providers, strongly supporting its widespread utilization both during and following the COVID-19 pandemic.

Bedside Ultrasound Versus Chest Radiography for Detection of Pulmonary Edema: A Prospective Cohort Study.

OBJECTIVES: Chest radiography has been the preferred imaging study to assess pulmonary congestion. However, chest radiography interpretation is influenced by the level of expertise and high interobserver variability. Lung ultrasound (US) may produce more objective findings through evaluation of vertical comet tail artifacts known as B-lines, which are created by a decrease in the ratio of alveolar air to fluid pulmonary content. Few studies have directly compared chest radiography to bedside US against a reference standard for the diagnosis of pulmonary edema. This study compared the sensitivity and specificity of bedside US and chest radiography in diagnosing pulmonary edema. METHODS: This prospective observational cohort study involved adult patients presenting to the emergency department of an urban tertiary hospital with dyspnea. The primary outcome was the presence or absence of pulmonary edema, as indicated by B-lines on a bedside lung US examination or radiologist-interpreted chest radiography. Patients underwent a US examination within about 1 hour of chest radiography. The final diagnosis from the discharge summary served as the reference standard. RESULTS: Ninety-nine patients were enrolled; 32.3% had congestive heart failure, and 40.4% had chronic obstructive pulmonary disease. Bedside US showed significantly higher sensitivity (96%) compared to chest radiography (65%; P < .001). Of 18 patients with negative radiographic findings and a discharge diagnosis of pulmonary edema, 16 (89%) had positive US findings (P < .001). CONCLUSIONS: Bedside US has the potential to identify pulmonary edema more accurately than chest radiography. As current practice within the United States uses chest radiography, reflecting American College of Cardiology Foundation/American Heart Association guidelines for management of heart failure, the results of this study warrant further evaluation.

Male-Centric and Female-Centric Pornography Consumption: Relationship With Sex Life and Attitudes in Young Adults.

Pornography availability has increased in recent years, and while there is plenty of speculation about its effects, empirical investigation about how porn influences our lives has yielded mixed results. Additionally, few studies have addressed the effects of specific pornography characteristics. Past research has shown that male-centric pornography can be related to negative outcomes, while female-centric pornography is related to more positive outcomes, particularly in women. The present survey study examined the relationship between pornography characteristics (male- and female-centric) and the self-reported attitudes and sexual experiences of men and women. Participants in the full sample were 195 men and 310 women who completed an online questionnaire. Although effect sizes were small, women who reported viewing pornography with more female-centric features also reported more positive effects of pornography on sex life and perceptions of the other gender. While men were more likely than women to report negative effects relating to pornography use on these same measures, there were very few reported negative effects of pornography overall. These findings demonstrate a small association between the use of female-centric pornography and more positive outcomes, particularly for women.

Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects.

PURPOSE: Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. METHODS: Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. RESULTS: Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87-91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. CONCLUSIONS: Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF.

Differences in Neural Response to Romantic Stimuli in Monogamous and Non-Monogamous Men.

In non-human animal research, studies comparing socially monogamous and promiscuous species of voles (Microtus) have identified some key neural differences related to monogamy and non-monogamy. Specifically, densities of the vasopressin V1a receptor and dopamine D2 receptors in subcortical reward-related and limbic areas of the brain have been linked to monogamous behavior in prairie voles (Microtus ochrogaster). Similar brain areas have been shown to be correlated with feelings of romantic love in monogamously pair-bonded humans. Humans vary in the degree to which they engage in (non-)monogamous behaviors. The present study examined the differences in neural activation in response to sexual and romantic stimuli in monogamous (n = 10) and non-monogamous (n = 10) men. Results indicated that monogamous men showed more reward-related neural activity when viewing romantic pictures compared to non-monogamous men. Areas with increased activation for monogamous men were all in the right hemisphere and included the thalamus, accumbens, striatum, pallidum, insula, and orbitofrontal cortex. There were no significant differences between groups in activation to sexual stimuli. These results demonstrate that the neural processing of romantic images is different for monogamous and non-monogamous men. There is some overlap in the neural areas showing increased activation in monogamous men in the present study and the neural areas that show differences in the vole models of monogamy and affiliation. Future research will be needed to clarify whether similar factors are contributing to the neural differences seen in monogamous and non-monogamous humans and voles.

Effect of evolocumab on cholesterol synthesis and absorption.

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in ß-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering.

Androgen deprivation therapy's impact on the mood of prostate cancer patients as perceived by patients and the partners of patients.

OBJECTIVE: To assess the relationship between of androgen deprivation therapy (ADT) and the mood of prostate cancer (PCa) patients and partners of PCa patients. METHODS: PCa patients (n = 295) and partners of patients (n = 84) completed an online survey assessing the patients' current mood and mood prior to treatment, relationship adjustment, and sexual function. We compared men on ADT to men who received non-hormonal treatments for their PCa. RESULTS: Patients currently treated with ADT (n = 82) reported worsened mood as measured by the Profile of Mood States compared to those not on ADT (n = 213). The negative impact of ADT on mood, however, was reduced in older patients. Partners of patients on ADT (n = 42) reported similar declines in the patient's mood that patients reported, but to a greater degree than patient-reported levels. CONCLUSIONS: Our data support ADT's impact on PCa patients' mood and verify that partners concurrently see the effects. The psychological changes related to ADT can impact relationships and affect the quality of life of both PCa patients and partners. Patients and their partners are likely to benefit from being well informed about the psychological effects of androgen deprivation on men beginning ADT. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The perspective of prostate cancer patients and patients' partners on the psychological burden of androgen deprivation and the dyadic adjustment of prostate cancer couples.

OBJECTIVE: Prostate cancer and its treatments, particularly androgen deprivation therapy (ADT), affect both patients and partners. This study assessed how prostate cancer treatment type, patient mood, and sexual function related to dyadic adjustment from patient and partner perspectives. METHODS: Men with prostate cancer (n = 206) and partners of men with prostate cancer (n = 66) completed an online survey assessing the patients' mood (profile of mood states short form), their dyadic adjustment (dyadic adjustment scale), and sexual function (expanded prostate cancer index composite). RESULTS: Analyses of covariance found that men on ADT reported better dyadic adjustment compared with men not on ADT. Erectile dysfunction was high for all patients, but a multivariate analysis of variance found that those on ADT experienced greater bother at loss of sexual function than patients not on ADT, suggesting that loss of libido when on ADT does not mitigate the psychological distress associated with loss of erections. In a multiple linear regression, patients' mood predicted their dyadic adjustment, such that worse mood was related to worse dyadic adjustment. However, more bother with patients' overall sexual function predicted lower relationship scores for the patients, while the patients' lack of sexual desire predicted lower dyadic adjustment for partners. CONCLUSIONS: Both patients and partners are impacted by the prostate cancer treatment effects on patients' psychological and sexual function. Our data help clarify the way that prostate cancer treatments can affect relationships and that loss of libido on ADT does not attenuate distress about erectile dysfunction. Understanding these changes may help patients and partners maintain a co-supportive relationship. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

CYP2C19 drug-drug and drug-gene interactions in ED patients.

BACKGROUND: CYP450 polymorphisms result in variable rates of drug metabolism. CYP drug-drug interactions can contribute to altered drug effectiveness and safety. STUDY OBJECTIVES: The primary objective was to determine the percentage of emergency department (ED) patients with cytochrome 2C19 (CYP2C19) drug-drug interactions. The secondary objective was to determine the prevalence of CYP2C19 polymorphisms in a US ED population. METHODS: We conducted a prospective observational study in an urban academic ED with 72,000 annual visits. Drug ingestion histories for the 48 hours preceding ED visit were obtained; each drug was coded as CYP2C19 substrate, inhibitor, inducer, or not CYP2C19 dependent. Ten percent of patients were randomized to undergo CYP2C19 genotyping using the Roche Amplichip. RESULTS: A total of 502 patients were included; 61% were female, 65% were white, and median age was 39 years (interquartile range, 22-53). One hundred thirty-one (26.1%) patients had taken at least 1 CYP2C19-dependent home drug. Eighteen (13.7%) patients who were already taking a CYP2C19-dependent drug were given or prescribed a CYP2C19-dependent drug while in the ED. Among the 53 patients genotyped, 52 (98%) were extensive metabolizers and 1 was a poor metabolizer. CONCLUSIONS: In a population of ED patients, more than a quarter had taken a CYP2C19-dependent drug in the preceding 48 hours, but few were given or prescribed another CYP2C19-dependent drug in the ED. On genotyping analysis, CYP2C19 polymorphisms were uncommon in our cohort. We conclude that changing prescribing practice due to CYP2C19 drug-drug interaction or genotype is unlikely to be useful in most US ED populations.

The relationship between daily hassles and sexual function in men and women.

Psychological stressors can interfere with sexual function through psychological and physiological mechanisms. Chronic stress, in particular, seems to have a negative effect on sexual functioning for men and women. The present study was designed to identify categories of stressors that contribute to sexual difficulties as well as assess the role of anxiety and depression in the relationship between stress and sexual function. Participants were recruited for an online survey in which they completed questionnaires on daily stressors, anxiety, depression, and sexual function. Results indicated that daily stressors predicted lower scores on sexual satisfaction for men and women and sexual activity for women. These effects were mediated by scores on the depression scale. Daily stressors, depression, and anxiety were highly correlated. A factor analysis of stressors resulted in 5 distinct categories of stressors. Of these, financial stressors and stressors related to low socioeconomic status were related to lower scores on all aspects of sexual functioning for women but not for men. Women's sexual functioning scores were more strongly related to stress and depression than men's scores. Results suggest that contextual factors (e.g., daily stressors, depression) are important considerations when assessing problems with sexual functioning.

Outcome of pure mucocele-like lesions diagnosed on breast core biopsy.

AIM: Current guidelines recommend that mucocele-like lesions (MLL) of the breast diagnosed on needle core biopsy (NCB) should be categorized as a lesion of uncertain malignant potential (B3). However, data on the outcome of MLL diagnosed on NCB remains limited due to the rarity of this lesion. The aim of this study was to assess the outcome of pure MLL without atypia diagnosed on NCB using a large series of cases and a review of the literature to provide evidence that can guide management. METHODS AND RESULTS: Patients who underwent diagnostic excision biopsy after a core biopsy diagnosis of MLL without atypia were identified from several centres. Two of 54 patients (4%) with MLL without atypia on core biopsy had ductal carcinoma in situ in the subsequent excision specimen. This is similar to the rate in previous studies of 4% (four of 106). If there is atypia in the core biopsy, previous studies found that the frequency of malignancy is much higher at 21% (seven of 33). CONCLUSIONS: Our results provide evidence that pure MLL without atypia diagnosed on NCB is usually associated with a benign outcome.

Chronic stress and sexual function in women.

INTRODUCTION: Chronic stress is known to have negative effects on reproduction, but little is known about how it affects the sexual response cycle. The present study examined the relationship between chronic stress and sexual arousal and the mechanisms that mediate this relationship. AIM: The aim of this study is to test the relationship between chronic stress and sexual arousal and identify mechanisms that may explain this relationship. We predicted that women experiencing high levels of chronic stress would show lower levels of genital arousal and dehydroepiandrosterone (DHEAS) and higher levels of cortisol and cognitive distraction compared with women with average levels of stress. METHODS: Women who were categorized as high in chronic stress (high stress group; n=15) or average in chronic stress (average stress group; n=15) provided saliva samples and watched an erotic film while having their genital and psychological arousal measured. MAIN OUTCOME MEASURES: Main outcome measures were vaginal pulse amplitude, psychological arousal, salivary cortisol, salivary DHEAS, and heart rate and compared them between women with high and average levels of chronic stress. RESULTS: Women in the high stress group had lower levels of genital, but not psychological arousal, had higher levels of cortisol, and reported more distraction during the erotic film than women in the average stress group. The main predictor of decreased genital sexual arousal was participants' distraction scores. CONCLUSIONS: High levels of chronic stress were related to lower levels of genital sexual arousal. Both psychological (distraction) and hormonal (increased cortisol) factors were related to the lower levels of sexual arousal seen in women high in chronic stress, but distraction was the only significant predictor when controlling for other variables.

Predictors of attrition from an expressive writing intervention for sexual abuse survivors.

This study examined predictors of attrition from a clinical trial examining the effects of an expressive writing intervention for sexual problems among female survivors of child sexual abuse. Participants were 124 women all reporting sexual difficulties, who were randomized to a trauma-focused condition (n = 45), an experimental sexual schema-focused condition (n = 37), or a control condition (n = 42). Thirty-five women (28%) dropped out before completing posttreatment assessments. Younger age, less education, and increased use of positive coping strategies were each independently associated with dropout. Results have implications for both researchers and clinicians working with this population, and it is hoped that these data can help bolster retention of those who are more likely to discontinue treatment.

Characterization and outcome of breast needle core biopsy diagnoses of lesions of uncertain malignant potential (B3) in abnormalities detected by mammographic screening.

In the setting of breast cancer screening, 5-9% of needle core biopsies are diagnosed as lesions of uncertain malignant potential (B3). The management of these lesions is potentially problematic as the data on their outcome remains limited. In our study, we aim to assess the outcome of screen-detected lesions diagnosed as B3 in a large series to validate previous studies and to characterize the malignant lesions detected after a B3 diagnosis. Therefore, the results of 1,025 needle core biopsies of women screened over a 7-year period (1999-2006) in two different regions in the UK with B3 diagnoses who underwent surgical excision were reviewed and compared to the final excision histology. Final histology showed that 25% of cases were malignant (17% ductal carcinoma in situ and 8% invasive). Predictors of malignancy included calcification on imaging and epithelial atypia on needle core biopsy particularly atypical ductal hyperplasia [positive predictive value 50%]. Pure flat epithelial atypia showed the lowest positive predictive value amongst all epithelial atypia groups (21%). The positive predictive value was low for complex sclerosing lesions (9%) and papillary lesions (13%) without epithelial atypia. Malignant tumors detected after B3 diagnosis showed favorable histological features, the majority were in situ, and most belonged to the low grade breast neoplasia family that is associated with indolent behavior. The underlying radiological abnormality was calcification in 44% of cases and the imaging classification was malignant/suspicious in 38%. In conclusion, our results further emphasize the heterogeneity of B3 lesions and that the likelihood of malignancy varies substantially between different histological subtypes. Malignancy is particularly associated with epithelial atypia suggesting the use of two categories of with and without epithelial atypia. Radiological findings provided useful information regarding the nature and outcome of B3 lesions.