Storage trends, usage and disposition outcomes following egg freezing.

RESEARCH QUESTION: What happens to eggs after egg freezing? DESIGN: A retrospective cohort study was performed spanning 2012-2022. Data were obtained from seven assisted reproductive technology clinics in Victoria, Australia. Aggregated, de-identified data were collected on cycles that resulted in egg freezing and the following outcomes, including treatment involving thawed eggs and disposition outcomes of surplus eggs. RESULTS: The number of patients with eggs in storage grew rapidly from 144 in 2012 to 2015 in 2022. In 2022, 73% of patients had stored their eggs for <5 years, 25% for 5-10 years, and 2% for ≥10 years. Most thaw cycles (600/645, 93%) involved eggs that had been frozen for <5 years, of which 47% had been frozen for <6 months. Overall, the live birth rate per initiated thaw cycle was 12%. Across the study period, 2800 eggs from 286 patients were either discarded, donated or exported. Of the 128 patients who discarded their eggs, 32% had stored their eggs for <5 years, 32% for 5-10 years and 36% for >10 years. Of the 23 patients who donated their eggs to someone else, all but four had stored their eggs for <5 years. No eggs were donated to research over the study period. CONCLUSIONS: This study shows that very few patients have made the decision to use or relinquish their eggs. Strategies may be needed to address the prolonged storage of surplus eggs, and ensure that patients are supported to make decisions regarding the fate of their eggs which align with their preferences and values.

Medicine in the marketplace: clinician and patient views on commercial influences on assisted reproductive technology.

RESEARCH QUESTION: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms? DESIGN: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis. RESULTS: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways - increasing sustainability, ensuring consistency in standards and providing patients with greater choice. Participants also considered commercial forces to have a number of negative impacts, including increased costs to government and patients; the excessive use of interventions that lack sufficient evidence to be considered part of standard care; inadequately informed consent (particularly with regard to financial information); and threats to patient-provider relationships and patient-centred care. Participants varied in whether they believed that professional self-regulation is sufficient. While recognizing the benefits of commercial investment in healthcare, many considered that regulatory reforms, as well as organizational cultural initiatives, are needed as means to ensure the primacy of patient well-being. CONCLUSIONS: The views expressed in this study should be systematically and critically examined to derive insights into how best to govern ART. These insights may also inform the design and delivery of other types of healthcare that are provided in the private sector.

Attitudes and barriers to breastfeeding among women at high-risk for not breastfeeding: a prospective observational study.

BACKGROUND: Rates of breastfeeding are lower among minority and underserved populations in the United States. Our study objective was to assess pregnant persons attitudes and barriers to breastfeeding among a cohort at high risk for not breastfeeding. METHODS: We disseminated the Iowa Infant Feeding Attitude Scale (IIFAS) to 100 pregnant persons at least 18 years of age attending a prenatal visit in a low-resource, academic practice in south-central Louisiana (Woman's Hospital). The IIFAS, as well as questions collecting information on breastfeeding experience and sociodemographic characteristics, were administered via interview. Medical records were reviewed to investigate associations between attitudes about breastfeeding in pregnancy and patient's feeding choices during the delivery hospital stay. Fisher exact tests and Wilcoxon rank-sum tests were used to assess associations between categorical and continuous variables respectively. RESULTS: Of the 98 participants who completed the study, 8% were Hispanic, 63% were Black, 95% were Medicaid eligible, and 50% were unemployed. 59% (n = 58) went on to breastfeed/combination breast-formula feed (called "Any-Breastfeeding Group") during the delivery stay. Total IIFAS score during pregnancy was significantly higher among those who went on to breastfeed during delivery hospital stay (Any-Breastfeeding Group vs. Formula-Feeding-Only Group: 58.9 ± 5.5 vs. 53.7 ± 6.2 respectively, p < 0.001). In the group that went on to only formula feed (Formula-Feeding-Only Group), only 4% agreed breastfeeding was more convenient when surveyed during pregnancy, compared to 45% of the Any-Breastfeeding Group. 60% of Formula-Feeding-Only Group agreed formula is as healthy as breast milk. CONCLUSION: The three major themes that coincided with favorability toward breastfeeding in the study, and can be addressed during prenatal counseling, are: mother-infant bonding, convenience, and health benefits. By identifying attitudes and barriers to breastfeeding for patients during pregnancy who went on to not breastfeed, directed educational opportunities can be developed to address these specific attitudes to ultimately increase breastfeeding initiation and continuation.

The risk of perinatal and cardiometabolic complications in pregnancies conceived by medically assisted reproduction.

PURPOSE: To examine the impact of medically assisted fertility treatments on the risk of developing perinatal and cardiometabolic complications during pregnancy and in-hospital deliveries. METHODS: We conducted a retrospective cohort study using medical health records of deliveries occurring in 2016-2022 at a women's specialty hospital in a southern state of the Unites States (US). Pregnancies achieved using medically assisted reproductive (MAR) techniques were compared with unassisted pregnancies using propensity score matching (PSM), based on demographic, preexisting health, and reproductive factors. Study outcomes included cesarean delivery, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), delivery complications, and postpartum readmission. We used Poisson regression with robust standard errors to generate risk ratios (RRs) and 95% confidence intervals (CIs) for all study outcomes. RESULTS: Among 57,354 deliveries, 586 (1.02%) pregnancies were achieved using MAR and 56,768 (98.98%) were unassisted ("non-MAR"). Compared to the non-MAR group, MAR pregnancies had significantly higher prevalence of all study outcomes, including GDM (15.9% vs. 11.2%, p < 0.001), HDP (28.2% vs. 21.1%, p < 0.001), cesarean delivery (56.1% vs. 34.6%, p < 0.001), delivery complications (10.9% vs. 6.8%, p = 0.03), and postpartum readmission (4.3% vs. 2.7%, p = 0.02). In a PSM sample of 584 MAR and 1,727 unassisted pregnancies, MAR was associated with an increased risk of cesarean delivery (RR = 1.11, 95% CI = 1.01-1.22); whereas IVF was associated with an increased risk of cesarean delivery (RR = 1.15, 95% CI = 1.03-1.28) and delivery complications (RR = 1.44, 95% CI = 1.04-2.01). CONCLUSIONS: Women who conceived with MAR were at increased risk of cesarean deliveries, and those who conceived with IVF were additionally at risk of delivery complications.

Care plan for individuals at risk for preeclampsia: shared approach to education, strategies for prevention, surveillance, and follow-up.

Preeclampsia is a multisystemic disorder of pregnancy that affects 250,000 pregnant individuals in the United States and approximately 10 million worldwide per annum. Preeclampsia is associated with substantial immediate morbidity and mortality but also long-term morbidity for both mother and offspring. It is now clearly established that a low dose of aspirin given daily, beginning early in pregnancy modestly reduces the occurrence of preeclampsia. Low-dose aspirin seems safe, but because there is a paucity of information about long-term effects on the infant, it is not recommended for all pregnant individuals. Thus, several expert groups have identified clinical factors that indicate sufficient risk to recommend low-dose aspirin preventive therapy. These risk factors may be complemented by biochemical and/or biophysical tests that either indicate increased probability of preeclampsia in individuals with clinical risk factors, or more importantly, identify increased likelihood in those without other evident risk. In addition, the opportunity exists to provide this population with additional care that may prevent or mitigate the short- and long-term effects of preeclampsia. Patient and provider education, increased surveillance, behavioral modification, and other approaches to improve outcomes in these individuals can improve the chance of a healthy outcome. We assembled a group with diverse, relevant expertise (clinicians, investigators, advocates, and public and private stakeholders) to develop a care plan in which providers and pregnant individuals at risk can work together to reduce the risk of preeclampsia and associated morbidities. The plan is for care of individuals at moderate to high risk for developing preeclampsia, sufficient to receive low-dose aspirin therapy, as identified by clinical and/or laboratory findings. The recommendations are presented using the GRADE methodology with the quality of evidence upon which each is based. In addition, printable appendices with concise summaries of the care plan's recommendations for patients and healthcare providers are provided. We believe that this shared approach to care will facilitate prevention of preeclampsia and its attendant short- and long-term morbidity in patients identified as at risk for development of this disorder.

Women's expectations about birth, requests for pain relief in labor and the subsequent development of birth dissonance and trauma.

BACKGROUND: Birth is a significant event in women's lives. As Mansfield notes (2008) many women aim for a birth that avoids pharmacological pain relief because they are advised it is better for them and their baby. For women having their first baby, this may not be realistic as 3/4 of primiparous women in Australia will use pharmacological pain relief. This study examines the expectations that a group of women had regarding pain relief, how these expectations developed and what happened to requests for pain relief in labour. METHODS: A longitudinal prospective study design was used to recruit 15 women who were having their first baby. Women having low risk pregnancies, hoping for a 'natural birth' (vaginal, no/minimal pharmacological pain relief) were eligible. A semi-structured interview tool was used across all three interviews that asked women about their expectations, then actual labour experience, pain management requests and how these were responded to by carers. Fifteen women were interviewed - at 36 weeks gestation; as soon after delivery of their baby as possible, then six months post-delivery (N = 43 interviews). Interviews were recorded and transcribed and coded by ES using NVivo software with hierarchical thematic analysis used. RESULTS: The study found that women appear to experience a mismatch between expectations they had developed pre-birth, versus actual experience. This appears to cause a specific form of dissonance - which we have termed 'birth dissonance' leaving them feeling traumatised post birth. This is because what women expected to happen in birth was often not realised. In particular, some women requested pain relief in birth and felt that their request was not responded to as hoped, and also seemed to develop post-birth trauma. We proposed that this may have resulted from dissonance arising from their expectations about being able to birth without significant pain relief. Interventions and technology may also contribute to this sense of mismatch and post-birth trauma. CONCLUSIONS: Low risk birthing women birthing in a hospital may have to engage with higher levels of technology, intervention and pain relief than that which they expected pre-birth. This could possibly be avoided with four simple changes. Firstly, better pre-birth education for women about how painful labor is likely to be. Secondly, pre-birth education which includes a detailed explanation of the utility of pharmacological and non-pharmacological pain relief. Thirdly, more egalitarian decision-making during labour and finally delivering upon women's requests for pain relief in labor, at the time that they ask for it. Further research is required to determine the extent of birth dissonance and how women making the transition to motherhood can avoid it.

Co-occurrence of depression, anxiety, and perinatal posttraumatic stress in postpartum persons.

BACKGROUND: The study aim was to describe the incidence of depression, anxiety, perinatal-post-traumatic stress disorder (PTSD), and their co-occurrences in the early postpartum period in a low-resource OB/GYN clinic serving majority Medicaid-eligible persons. We hypothesized that postpartum persons screening positive for depression will have an increased risk of a positive screen for anxiety and perinatal PTSD. METHODS: A retrospective study of postpartum persons receiving care in Baton Rouge, Louisiana was conducted using responses abstracted from the electronic medical record (EMR) of the Patient Health Questionnaire-9 (PHQ9), Generalized Anxiety Disorder-7 (GAD7), and Perinatal Post Traumatic Stress Disorder Questionnaire-II (PPQII). Categorical distributions were compared using Fisher exact tests, while t-tests were used to compare continuous covariates. Multivariable logistic regression was used to predict anxiety (GAD7) and perinatal PTSD (PPQII) scores while adjusting for potential confounders, as well as to predict continuous PPQII and GAD7 based on continuous PHQ9 scores. RESULTS: There were 613 birthing persons 4-12 weeks postpartum that completed mental health screening (PHQ9, GAD7, and PPQII) between November 2020 and June 2022 as part of routine postpartum care in the clinic. The incidence of screening positive for symptoms of depression (PHQ9 > 4) was 25.4% (n = 156), while the incidence of positive screening for symptoms of anxiety (GAD7 > 4) and perinatal PTSD (PPQII [Formula: see text] 19) were 23.0% (n = 141) and 5.1% (n = 31) respectively. Postpartum patients with mild anxiety or more (i.e. GAD7 > 4) had 26 times higher odds of screening positive for symptoms of depression (PHQ9 > 4) (adjusted odds ratio [aOR] 26.3; 95% confidence interval [CI] 15.29-46.92; p < 0.001). Postpartum persons with a PPQII score indicating symptoms of perinatal PTSD (PPQII [Formula: see text] 19) had 44 times higher odds of screening positive for symptoms of depression (PHQ > 4) (aOR 44.14; 95%CI 5.07-5856.17; p < 0.001). CONCLUSIONS: Depression, anxiety, and perinatal PTSD are each independent risk factors for each other. To comply with the American College of Obstetricians and Gynecologists (ACOG) recommendations, providers should universally screen postpartum persons with validated screening tools for mood disturbances. However, if a complete full mood assessment is not feasible, this study provides evidence to support screening patients for depression, and if the patient screens positive, prompt additional screening for anxiety and perinatal PTSD.

Social distancing and mental health among pregnant women during the coronavirus pandemic.

BACKGROUND: The effect of social distancing due to the COVID-19 pandemic on the mental health of pregnant women is of particular concern, given potential effects on physical health, family functioning, and child development. METHODS: Pregnant women were recruited for the "Implications of and Experiences Surrounding being Pregnant during the COVID-19 Pandemic" study at Woman's Hospital in Baton Rouge, Louisiana. Participants enrolled at any point during their pregnancy and surveys were delivered weekly until the participant indicated that she had delivered her baby; a postpartum survey followed four weeks after delivery. This analysis includes 1037 participants with baseline, 596 with follow-up, and 302 with postpartum surveys. Questions on social distancing behaviors were asked at baseline and grouped based on whether they involved social distancing from work, friends and family, or public places. Symptoms of anxiety, stress, depression, and pregnancy-related anxiety were measured. Each type of social distancing was examined as a predictor of mental health using linear model with control for confounders. RESULTS: The study population was largely white (84.1%), married (81.8%), and educated (76.2% with a bachelor's or higher degree). Women who were younger, Black, unmarried, or had less education or income reported fewer social distancing behaviors. Mean anxiety score in the highest quartile of overall social distancing was 8.3 (SD 5.6), while in the lowest quartile it was 6.0 (SD 5.0) (p < 0.01), while perceived stress postpartum and pregnancy-related stress were not associated with social distancing. Associations were substantially diminished when controlled for baseline levels of anxiety symptoms. CONCLUSIONS: Greater social distancing was associated with more anxiety symptoms, but worse mental health, particularly anxiety, may also have contributed to greater social distancing behaviors.

ACGME Program Requirements for Surgical Specialties: How Do Dermatology and MSDO Stack Up?

Dermatology and micrographic surgery and dermatologic oncology (MSDO) are two areas of medicine where surgical procedures play an important role both in training and practice. We sought to determine how dermatology and MSDO compare to ACGME surgical specialties with regard to surgical curriculum and case log requirements. We found that the surgical curriculums for dermatology and MSDO are similar to those of our surgical colleagues in ophthalmology, obstetrics, and gynecology. They are similar in that none require general surgery rotations, a general surgery postgraduate year 1 is not required, and all surgical experience can be obtained within each respective specialty residency training program. Regarding case log requirements, MSDO was found to have numerical case log requirements comparable to those of ACGME surgical specialties. Dermatology case log requirements were on the low end of the surgical spectrum. In dermatology and MSDO, surgical training is well integrated into the programs and case log requirements. They represent two of the many areas where medicine and surgery combine in the name of patient care. J Drugs Dermatol. 2023;22(1): doi:10.36849/JDD.6886.

Topical Anesthetic Use in Cosmetic Dermatology.

In today's society, there is growing interest in outpatient cosmetic procedures. Topical anesthetics are commonly used as anesthesia for these procedures. They can be used alone or part of a multi-pronged anesthetic approach. Topical anesthetics have many benefits, but they also have some negatives including risk of toxicity. For this paper, we focused on the role of topical anesthetics in cosmetic dermatology. We surveyed cosmetic dermatologists on the use of topical anesthetics in their practices. We found that the most popular topical anesthetic was benzocaine 20% / lidocaine 6% / tetracaine 4%. When asked for which procedures topical anesthetics are used for anesthesia, the most frequent responses were fractionally ablative lasers and fractionally non-ablative lasers. Though the majority of surveyed dermatologists have not had issues with the topical anesthetic, a portion had experienced adverse events in their patients. Topical anesthetics play an important role in cosmetic dermatology, allowing cosmetic procedures to take place in ways that are both comfortable for patients and allow patients to avoid more involved types of anesthesia. This is a growing area of cosmetic dermatology that requires additional research. J Drugs Dermatol. 2023;22(3): doi:10.36849/JDD.6978.

Inclusion of binary proxy variables in logistic regression improves treatment effect estimation in observational studies in the presence of binary unmeasured confounding variables.

We present a simulation study and application that shows inclusion of binary proxy variables related to binary unmeasured confounders improves the estimate of a related treatment effect in binary logistic regression. The simulation study included 60,000 randomly generated parameter scenarios of sample size 10,000 across six different simulation structures. We assessed bias by comparing the probability of finding the expected treatment effect relative to the modeled treatment effect with and without the proxy variable. Inclusion of a proxy variable in the logistic regression model significantly reduced the bias of the treatment or exposure effect when compared to logistic regression without the proxy variable. Including proxy variables in the logistic regression model improves the estimation of the treatment effect at weak, moderate, and strong association with unmeasured confounders and the outcome, treatment, or proxy variables. Comparative advantages held for weakly and strongly collapsible situations, as the number of unmeasured confounders increased, and as the number of proxy variables adjusted for increased.

Breast MRI Background Parenchymal Enhancement Categorization Using Deep Learning: Outperforming the Radiologist.

BACKGROUND: Background parenchymal enhancement (BPE) is assessed on breast MRI reports as mandated by the Breast Imaging Reporting and Data System (BI-RADS) but is prone to inter and intrareader variation. Semiautomated and fully automated BPE assessment tools have been developed but none has surpassed radiologist BPE designations. PURPOSE: To develop a deep learning model for automated BPE classification and to compare its performance with current standard-of-care radiology report BPE designations. STUDY TYPE: Retrospective. POPULATION: Consecutive high-risk patients (i.e. >20% lifetime risk of breast cancer) who underwent contrast-enhanced screening breast MRI from October 2013 to January 2019. The study included 5224 breast MRIs, divided into 3998 training, 444 validation, and 782 testing exams. On radiology reports, 1286 exams were categorized as high BPE (i.e., marked or moderate) and 3938 as low BPE (i.e., mild or minimal). FIELD STRENGTH/SEQUENCE: A 1.5 T or 3 T system; one precontrast and three postcontrast phases of fat-saturated T1-weighted dynamic contrast-enhanced imaging. ASSESSMENT: Breast MRIs were used to develop two deep learning models (Slab artificial intelligence (AI); maximum intensity projection [MIP] AI) for BPE categorization using radiology report BPE labels. Models were tested on a heldout test sets using radiology report BPE and three-reader averaged consensus as the reference standards. STATISTICAL TESTS: Model performance was assessed using receiver operating characteristic curve analysis. Associations between high BPE and BI-RADS assessments were evaluated using McNemar's chi-square test (α* = 0.025). RESULTS: The Slab AI model significantly outperformed the MIP AI model across the full test set (area under the curve of 0.84 vs. 0.79) using the radiology report reference standard. Using three-reader consensus BPE labels reference standard, our AI model significantly outperformed radiology report BPE labels. Finally, the AI model was significantly more likely than the radiologist to assign "high BPE" to suspicious breast MRIs and significantly less likely than the radiologist to assign "high BPE" to negative breast MRIs. DATA CONCLUSION: Fully automated BPE assessments for breast MRIs could be more accurate than BPE assessments from radiology reports. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Am I safe? An Interpretative Phenomenological Analysis of Vulnerability as Experienced by Patients With Complications Following Surgery.

Abdominal surgery carries with it risks of complications. Little is known about patients' experiences of post-surgical deterioration. There is a real need to understand the psychosocial as well as the biological aspects of deterioration in order to improve care and outcomes for patients. Drawing on in-depth interviews with seven abdominal surgery survivors, we present an idiographic account of participants' experiences, situating their contribution to safety within their personal lived experiences and meaning-making of these episodes of deterioration. Our analysis reveals an overarching group experiential theme of vulnerability in relation to participants' experiences of complications after abdominal surgery. This encapsulates the uncertainty of the situation all the participants found themselves in, and the nature and seriousness of their health conditions. The extent of participants' vulnerability is revealed by detailing how they made sense of their experience, how they negotiated feelings of (un)safety drawing on their relationships with family and staff and the legacy of feelings they were left with when their expectations of care (care as imagined) did not meet the reality of their experiences (care as received). The participants' experiences highlight the power imbalance between patients and professionals in terms of whose knowledge counts within the hospital context. The study reveals the potential for epistemic injustice to arise when patients' concerns are ignored or dismissed. Our data has implications for designing strategies to enable escalation of care, both in terms of supporting staff to deliver compassionate care, and in strengthening patient and family involvement in rescue processes.

The impact of scaling up access to treatment and imaging modalities on global disparities in breast cancer survival: a simulation-based analysis.

BACKGROUND: Female breast cancer is the most commonly diagnosed cancer in the world, with wide variations in reported survival by country. Women in low-income and middle-income countries (LMICs) in particular face several barriers to breast cancer services, including diagnostics and treatment. We aimed to estimate the potential impact of scaling up the availability of treatment and imaging modalities on breast cancer survival globally, together with improvements in quality of care. METHODS: For this simulation-based analysis, we used a microsimulation model of global cancer survival, which accounts for the availability and stage-specific survival impact of specific treatment modalities (chemotherapy, radiotherapy, surgery, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single-photon emission computed tomography [SPECT]), and quality of cancer care, to simulate 5-year net survival for women with newly diagnosed breast cancer in 200 countries and territories in 2018. We calibrated the model to empirical data on 5-year net breast cancer survival in 2010-14 from CONCORD-3. We evaluated the potential impact of scaling up specific imaging and treatment modalities and quality of care to the mean level of high-income countries, individually and in combination. We ran 1000 simulations for each policy intervention and report the means and 95% uncertainty intervals (UIs) for all model outcomes. FINDINGS: We estimate that global 5-year net survival for women diagnosed with breast cancer in 2018 was 67·9% (95% UI 62·9-73·4) overall, with an almost 25-times difference between low-income (3·5% [0·4-10·0]) and high-income (87·0% [85·6-88·4]) countries. Among individual treatment modalities, scaling up access to surgery alone was estimated to yield the largest survival gains globally (2·7% [95% UI 0·4-8·3]), and scaling up CT alone would have the largest global impact among imaging modalities (0·5% [0·0-2·0]). Scaling up a package of traditional modalities (surgery, chemotherapy, radiotherapy, ultrasound, and x-ray) could improve global 5-year net survival to 75·6% (95% UI 70·6-79·4), with survival in low-income countries improving from 3·5% (0·4-10·0) to 28·6% (4·9-60·1). Adding concurrent improvements in quality of care could further improve global 5-year net survival to 78·2% (95% UI 74·9-80·4), with a substantial impact in low-income countries, improving net survival to 55·3% (42·2-67·8). Comprehensive scale-up of access to all modalities and improvements in quality of care could improve global 5-year net survival to 82·3% (95% UI 79·3-85·0). INTERPRETATION: Comprehensive scale-up of treatment and imaging modalities, and improvements in quality of care could improve global 5-year net breast cancer survival by nearly 15 percentage points. Scale-up of traditional modalities and quality-of-care improvements could achieve 70% of these total potential gains, with substantial impact in LMICs, providing a more feasible pathway to improving breast cancer survival in these settings even without the benefits of future investments in targeted therapy and advanced imaging. FUNDING: Harvard T H Chan School of Public Health, and National Cancer Institute P30 Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center.

l-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia.

Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J C1q-/- preeclampsia-like mouse model. l-Citrulline is a nonessential amino acid that is converted to l-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO)-mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to C1q-/- male mice, and a subset of dams was supplemented with l-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 mo of age. Main findings show that l-citrulline reduced blood pressure, increased vascular glycocalyx volume, and rescued ex-vivo vascular function at gestation day 17.5 in this preeclampsia-like model. The vascular benefit of l-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 mo of age. l-Citrulline-mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, l-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health, which may have translational implications for improved maternal cardiovascular health.

Tumor-Nipple Distance of ≥ 1 cm Predicts Negative Nipple Pathology After Neoadjuvant Chemotherapy.

BACKGROUND: As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS-) in women undergoing total mastectomy after NAC. METHODS: Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS- was examined and the accuracy of 1 cm TND on imaging for predicting NS- was determined. RESULTS: Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p < 0.05). The likelihood of NS- was higher with increasing TND on pre- and post-NAC imaging (p < 0.05). TND ≥ 1 cm predicted NS- in 97% and 95% of breasts on pre- and post-NAC imaging, respectively. CONCLUSIONS: Increasing TND was associated with a higher likelihood of NS-. A TND ≥ 1 cm on pre- or post-NAC imaging is highly predictive of NS- and could be used to determine eligibility for nipple-sparing mastectomy after NAC.

Can Follow-up be Avoided for Probably Benign US Masses with No Enhancement on MRI?

OBJECTIVES: To assess whether no enhancement on pre-treatment MRI can rule out malignancy of additional US mass(es) initially assessed as BI-RADS 3 or 4 in women with newly diagnosed breast cancer. METHODS: This retrospective study included consecutive women from 2010-2018 with newly diagnosed breast cancer; at least one additional breast mass (distinct from index cancer) assigned a BI-RADS 3 or 4 on US; and a bilateral contrast-enhanced breast MRI performed within 90 days of US. All malignant masses were pathologically proven; benign masses were pathologically proven or defined as showing at least 2 years of imaging stability. Incidence of malignant masses and NPV were calculated on a per-patient level using proportions and exact 95% CIs. RESULTS: In 230 patients with 309 additional masses, 140/309 (45%) masses did not enhance while 169/309 (55%) enhanced on MRI. Of the 140 masses seen in 105 women (mean age, 54 years; range 28-82) with no enhancement on MRI, all had adequate follow-up and 140/140 (100%) were benign, of which 89/140 (63.6%) were pathologically proven and 51/140 (36.4%) demonstrated at least 2 years of imaging stability. Pre-treatment MRI demonstrating no enhancement of US mass correlate(s) had an NPV of 100% (95% CI 96.7-100.0). CONCLUSIONS: All BI-RADS 3 and 4 US masses with a non-enhancing correlate on pre-treatment MRI were benign. The incorporation of MRI, when ordered by the referring physician, may decrease unnecessary follow-up imaging and/or biopsy if the initial US BI-RADS assessment and management recommendation were to be retrospectively updated. KEY POINTS: • Of 309 BI-RADS 3 or 4 US masses with a corresponding mass on MRI, 140/309 (45%) demonstrated no enhancement whereas 169/309 (55%) demonstrated enhancement • All masses classified as BI-RADS 3 or 4 on US without enhancement on MRI were benign • MRI can rule out malignancy in non-enhancing US masses with an NPV of 100.

A qualitative study of organisational response to national quality standards for 7-day services in English hospitals.

BACKGROUND: National standards are commonly used as an improvement strategy in healthcare, but organisations may respond in diverse and sometimes negative ways to external quality demands. This paper describes how a sample of NHS hospital trusts in England responded to the introduction of national standards for 7-day services (7DS), from an organisational behaviour perspective. METHODS: We conducted 43 semi-structured interviews with executive/director level and clinical staff, in eight NHS trusts that varied in size, location, and levels of specialist staffing at weekends. We explored approaches to implementing standards locally, and the impact of organisational culture and local context on organisational response. RESULTS: Senior staff in the majority of trusts described a focus on hitting targets and achieving compliance with the standards. Compliance-based responses were associated with a hierarchical organisational culture and focus on external performance. In a minority of trusts senior staff described mobilising commitment-based strategies. In these trusts senior staff reframed the external standards in terms of organisational values, and used co-operative strategies for achieving change. Trusts that took a commitment-based approach tended to be described as having a developmental organisational culture and a history of higher performance across the board. Audit data on 7DS showed improvement against standards for most trusts, but commitment-focused trusts were less likely to demonstrate improvements on the 7DS audit. The ability of trusts to respond to external standards was limited when they were under pressure due to a history of overall poor performance or resource limitations. CONCLUSIONS: National standards and audit for service-level improvement generate different types of response in different local settings. Approaches to driving improvement nationally need to be accompanied by resources and tailored support for improvement, taking into account local context and organisational culture.

Using the CNE as an Innovative Strategy to Support Junior Nursing Faculty Transitioning From Clinical Practice.

ABSTRACT: For new nurse educators, the certified nurse educator credential can be more than a mark of expertise. This article explains how two junior nurse faculty discovered that preparation for certification facilitated the change process from clinician to academic nurse educator. We describe barriers overcome on the path to certification and highlight key factors for attaining success. The important fruits of certification are explored, and recommendations for professional development for new nurse educators are offered.

A machine learning model that classifies breast cancer pathologic complete response on MRI post-neoadjuvant chemotherapy.

BACKGROUND: For breast cancer patients undergoing neoadjuvant chemotherapy (NAC), pathologic complete response (pCR; no invasive or in situ) cannot be assessed non-invasively so all patients undergo surgery. The aim of our study was to develop and validate a radiomics classifier that classifies breast cancer pCR post-NAC on MRI prior to surgery. METHODS: This retrospective study included women treated with NAC for breast cancer from 2014 to 2016 with (1) pre- and post-NAC breast MRI and (2) post-NAC surgical pathology report assessing response. Automated radiomics analysis of pre- and post-NAC breast MRI involved image segmentation, radiomics feature extraction, feature pre-filtering, and classifier building through recursive feature elimination random forest (RFE-RF) machine learning. The RFE-RF classifier was trained with nested five-fold cross-validation using (a) radiomics only (model 1) and (b) radiomics and molecular subtype (model 2). Class imbalance was addressed using the synthetic minority oversampling technique. RESULTS: Two hundred seventy-three women with 278 invasive breast cancers were included; the training set consisted of 222 cancers (61 pCR, 161 no-pCR; mean age 51.8 years, SD 11.8), and the independent test set consisted of 56 cancers (13 pCR, 43 no-pCR; mean age 51.3 years, SD 11.8). There was no significant difference in pCR or molecular subtype between the training and test sets. Model 1 achieved a cross-validation AUROC of 0.72 (95% CI 0.64, 0.79) and a similarly accurate (P = 0.1) AUROC of 0.83 (95% CI 0.71, 0.94) in both the training and test sets. Model 2 achieved a cross-validation AUROC of 0.80 (95% CI 0.72, 0.87) and a similar (P = 0.9) AUROC of 0.78 (95% CI 0.62, 0.94) in both the training and test sets. CONCLUSIONS: This study validated a radiomics classifier combining radiomics with molecular subtypes that accurately classifies pCR on MRI post-NAC.