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Intimate partner violence is an ongoing issue in South Africa, which has the highest rates of violence against women and girls in the world. Intimate partner violence is common in Limpopo, where women, including university students, experience elevated rates of violent crime. This qualitative study was conducted to examine university students' perspectives regarding intimate partner violence among their peers. A culturally tailored vignette was used to prompt reflection from 38 female university students in Limpopo. Audiotaped responses to the vignette were transcribed, coded and analysed using thematic analysis. Four main themes were developed from participants' responses to the vignette: cultural beliefs, the university's role in intimate partner violence, likely outcomes of intimate partner violence, and future interventions. Intimate partner violence was seen as a common problem within the university. Students' responses indicated that cultural beliefs perpetuated violence against women, with women entering and remaining in abusive relationships for financial security or resources such as housing. Students also reported lack of adequate on-campus housing options, limited knowledge of intimate partner violence, and few actions to reduce intimate partner violence, all of which placed then at heightened risk of intimate partner violence.

Stressful conditions within disadvantaged neighborhoods may shape unhealthy alcohol use and related harms. Yet, associations between neighborhood disadvantage and more severe unhealthy alcohol use are underexplored, particularly for subpopulations. Among national Veterans Health Administration (VA) patients (2013-2017), we assessed associations between neighborhood disadvantage and multiple alcohol-related outcomes and examined moderation by sociodemographic factors.Electronic health record data were extracted for VA patients with a routine Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screen. Patient addresses were linked by census block group to the Area Deprivation Index (ADI), dichotomized at the 85th percentile, and examined in quintiles for sensitivity analyses. Using modified Poisson generalized estimating equations models, we estimated associations between neighborhood disadvantage and five outcomes: unhealthy alcohol use (AUDIT-C ≥ 5), any past-year heavy episodic drinking (HED), severe unhealthy alcohol use (AUDIT-C ≥ 8), alcohol use disorder (AUD) diagnosis, and alcohol-specific conditions diagnoses. Moderation by gender, race/ethnicity, and rurality was tested using multiplicative interaction.Among 6,381,033 patients, residence in a highly disadvantaged neighborhood (ADI ≥ 85th percentile) was associated with a higher likelihood of unhealthy alcohol use (prevalence ratio [PR] = 1.06, 95% CI [1.05, 1.07]), severe unhealthy alcohol use (PR = 1.14, 95% CI [1.12, 1.15]), HED (PR = 1.04, 95% CI [1.03, 1.05]), AUD (PR = 1.14, 95% CI [1.13, 1.15]), and alcohol-specific conditions (PR = 1.21, 95% CI [1.18, 1.24]). Associations were larger for Black and American Indian/Alaska Native patients compared with White patients and for urban compared with rural patients. There was mixed evidence of moderation by gender.Neighborhood disadvantage may play a role in unhealthy alcohol use in VA patients, particularly those of marginalized racialized groups and those residing in urban areas.

Anti-programmed cell death protein 1 (PD1) antibodies, pembrolizumab and nivolumab, alone or in combination with ipilimumab, have become standard treatment for melanoma and multiple other malignancies. Neurological adverse effects are rare and have not been well characterized to date. Patients who developed neurological adverse effects while being treated with PD1, alone or in combination with ipilimumab, were retrospectively identified from 10 cancer centers. Fifty-eight patients were included, and the median time from treatment initiation to development of neurological adverse effects was 7 weeks (range, 1-86.5 weeks). Thirty-seven (64%) toxicities affected the peripheral nervous system. Fifty (86%) patients were treated with corticosteroids, with 22 (37%) patients requiring further immunomodulation including intravenous immunoglobulin (16), plasmapheresis (7), mycophenolate mofetil (4), cyclophosphamide (1), and rituximab (1). Twenty-seven (46%) had a complete resolution of their neurological symptoms, and two (4%) patients died secondary to complications from their neurological adverse effects. The response rate of the cancer to immunotherapy was 78%, and the median progression free survival was not reached. Neurological adverse effects can occur with PD1 treatment, do not appear to impact treatment response, but may be irreversible or worsen in some patients. Management may require immunomodulation beyond corticosteroids.

Objectives Racial and socioeconomic disparities in the incidence of Legionnaires’ disease have been documented for the past 2 decades; however, the social determinants of health (SDH) that contribute to these disparities are not well studied. The objective of this narrative review was to characterize SDH to inform efforts to reduce disparities in the incidence of Legionnaires’ disease. Methods We conducted a narrative review of articles published from January 1979 through October 2019 that focused on disparities in the incidence of Legionnaires’ disease and pneumonia (inclusive of bacterial pneumonia and/or community-acquired pneumonia) among adults and children (excluding articles that were limited to people aged Results Of the 19 articles reviewed, multiple articles examined disparities in incidence of Legionnaires’ disease and pneumonia related to economic stability/income (n = 13) and comorbidities (n = 10), and fewer articles incorporated SDH variables related to education (n = 3), social support (none), health care access (n = 1), and neighborhood and built environment (n = 6) in their analyses. Conclusions Neighborhood and built-environment factors such as housing, drinking water infrastructure, and pollutant exposures represent critical partnership and research opportunities. More research that incorporates SDH and multilevel, cross-sector interventions is needed to address disparities in Legionnaires’ disease incidence.

PURPOSE Currently, there are no robust biomarkers that predict immunotherapy outcomes in metastatic melanoma. We sought to build multivariable predictive models for response and survival to anti-programmed cell death protein 1 (anti–PD-1) monotherapy or in combination with anticytotoxic T-cell lymphocyte-4 (ipilimumab [IPI]; anti–PD-1 ± IPI) by including routine clinical data available at the point of treatment initiation. METHODS One thousand six hundred forty-four patients with metastatic melanoma treated with anti–PD-1 ± IPI at 16 centers from Australia, the United States, and Europe were included. Demographics, disease characteristics, and baseline blood parameters were analyzed. The end points of this study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The final predictive models for ORR, PFS, and OS were determined through penalized regression methodology (least absolute shrinkage and selection operator method) to select the most significant predictors for all three outcomes (discovery cohort, N = 633). Each model was validated internally and externally in two independent cohorts (validation-1 [N = 419] and validation-2 [N = 592]) and nomograms were created. RESULTS The final model for predicting ORR (area under the curve [AUC] = 0.71) in immunotherapy-treated patients included the following clinical parameters: Eastern Cooperative Oncology Group Performance Status, presence/absence of liver and lung metastases, serum lactate dehydrogenase, blood neutrophil-lymphocyte ratio, therapy (monotherapy/combination), and line of treatment. The final predictive models for PFS (AUC = 0.68) and OS (AUC = 0.77) included the same variables as those in the ORR model (except for presence/absence of lung metastases), and included presence/absence of brain metastases and blood hemoglobin. Nomogram calculators were developed from the clinical models to predict outcomes for patients with metastatic melanoma treated with anti–PD-1 ± IPI. CONCLUSION Newly developed combinations of routinely collected baseline clinical factors predict the response and survival outcomes of patients with metastatic melanoma treated with immunotherapy and may serve as valuable tools for clinical decision making.

Postgraduate training programmes rely on faculty to meet core educational needs, including simulation. Time is arguably the most valuable resource for academic physicians, which presents a challenge for recruiting faculty to provide extra-clinical teaching. To increase faculty engagement in simulation-based education (SBE), we first identified barriers to participation. Next, we sought to overcome barriers using a self-determination theory (SDT) framework to increase motivation using strategies that addressed faculty autonomy, competence and relatedness.Faculty from a single department of emergency medicine were surveyed about factors influencing participation in SBE. Responses were grouped into themes and used to develop the intervention-a faculty support bundle-to overcome common barriers and promote participation. Supports focused on course materials, organisational consistency and peer recognition. Faculty participation in SBE pre- and post-implementation of the support bundle was analysed via chi-squared analysis. Faculty who delivered SBE were resurveyed after the implementation phase to explore how the support bundle affected their experience.Initial survey response was 41%. Reported barriers to participation in SBE included scheduling issues, preparation time, competing responsibilities, lack of confidence with simulation and lack of interest. Twenty-four faculty participated in SBE during the pre-implementation phase, compared to 39 post implementation (p = 0.03).The faculty support bundle increases faculty participation in SBE. Strategies focused on internal motivators identified using an SDT framework. In contrast to traditional external motivators, these were no cost interventions. Those seeking to increase faculty participation in SBE should consider implementing similar strategies.

Although incivility in nursing education is linked with negative physical and psychological effects on students, it is unclear how resilience and stress interact and relate to student incivility. The purpose was to understand the role of resilience and stress with peer incivility in a sample of prelicensure nursing students during coronavirus disease 2019. The study design was cross-sectional and correlational. Data were from an online survey administered to undergraduate nursing students of one college of nursing in a southwestern US state during September-October 2020. In a sample of 490 students, ordinal regression model results supported that including a stress and resilience interaction term resulted in a nonsignificant effect of stress and resilience, as the main effect correlates on low-level uncivil student behavior. More research is needed to understand the prevalence of stress and resilience at different points in prelicensure nursing education so that targeted interventions can be developed and deployed to assist students.

Legionella pneumophila is the cause of Legionnaires’ disease, a life-threatening pneumonia that occurs after inhalation of aerosolized water containing the bacteria. Legionella growth occurs in stagnant, warm-to-hot water (77°F–113°F) that is inadequately disinfected. Piped hot spring water in Hot Springs National Park, Arkansas, USA, has naturally high temperatures (>135°F) that prevent Legionella growth, and Legionnaires’ disease has not previously been associated with the park or other hot springs in the United States. During 2018–2019, Legionnaires’ disease occurred in 5 persons after they visited the park; 3 of these persons were potentially exposed in spa facilities that used untreated hot spring water. Environmental testing revealed Legionella bacteria in piped spring water, including 134°F stagnant pipe water. These findings underscore the importance of water management programs to reduce Legionella growth in plumbing through control activities such as maintaining hot water temperatures, reducing stored water age, and ensuring adequate water flow.

Pregnancy-related complaints are a significant driver of emergency room (ER) utilization among women. Because of additional time for patient education and provider relationships, group prenatal care may reduce ER visits among pregnant women by helping them identify appropriate care settings, improving understanding of common pregnancy discomforts, and reducing risky health behaviors. We conducted a retrospective cohort study, utilizing Medicaid claims and birth certificate data from a statewide expansion of group care, to compare ER utilization between pregnant women participating in group prenatal care and individual prenatal care. Using propensity score matching methods, we found that group care was associated with a significant reduction in the likelihood of having any ER utilization (–5.9% among women receiving any group care and –6.0% among women attending at least five group care sessions). These findings suggest that group care may reduce ER utilization among pregnant women and encourage appropriate health care utilization during pregnancy.

In the era of data-driven medicine, rapid access and accurate interpretation of medical images are becoming increasingly important. The DICOM Image ANalysis and Archive (DIANA) system is an open-source, lightweight, and scalable Python interface that enables users to interact with hospital Picture Archiving and Communications Systems (PACS) to access such data. In this work, DIANA functionality was detailed and evaluated in the context of retrospective PACS data retrieval and two prospective clinical artificial intelligence (AI) pipelines: bone age (BA) estimation and intra-cranial hemorrhage (ICH) detection. DIANA orchestrates activity beginning with post-acquisition study discovery and ending with online notifications of findings. For AI applications, system latency (exam completion to system report time) was quantified and compared to that of clinicians (exam completion to initial report creation time). Mean DIANA latency was 9.04 ± 3.83 and 20.17 ± 10.16 min compared to clinician latency of 51.52 ± 58.9 and 65.62 ± 110.39 min for BA and ICH, respectively, with DIANA latencies being significantly lower (p

Aims To explore factors associated with nurses' moral distress during the first COVID-19 surge and their longer-term mental health. Design Cross-sectional, correlational survey study. Methods Registered nurses were surveyed in September 2020 about their experiences during the first peak month of COVID-19 using the new, validated, COVID-19 Moral Distress Scale for Nurses. Nurses' mental health was measured by recently experienced symptoms. Analyses included descriptive statistics and regression analysis. Outcome variables were moral distress and mental health. Explanatory variables were frequency of COVID-19 patients, leadership communication and personal protective equipment/cleaning supplies access. The sample comprised 307 nurses (43% response rate) from two academic medical centres. Results Many respondents had difficulty accessing personal protective equipment. Most nurses reported that hospital leadership communication was transparent, effective and timely. The most distressing situations were the transmission risk to nurses' family members, caring for patients without family members present, and caring for patients dying without family or clergy present. These occurred occasionally with moderate distress. Nurses reported 2.5 days each in the past week of feeling anxiety, withdrawn and having difficulty sleeping. Moral distress decreased with effective communication and access to personal protective equipment. Moral distress was associated with longer-term mental health. Conclusion Pandemic patient care situations are the greatest sources of nurses' moral distress. Effective leadership communication, fewer COVID-19 patients, and access to protective equipment decrease moral distress, which influences longer-term mental health. Impact Little was known about the impact of COVID-19 on nurses' moral distress. We found that nurses' moral distress was associated with the volume of care for infected patients, access to personal protective equipment, and communication from leaders. We found that moral distress was associated with longer-term mental health. Leaders should communicate transparently to decrease nurses' moral distress and the negative effects of global crises on nurses' longer-term mental health.

Background/Objective Parents shape children’s early experiences with food, influencing what is served, children’s food choices, and how much children eat. Responsive parenting (RP) interventions such as INSIGHT have improved maternal infant feeding practices, but have only been tested among predominantly White families. This secondary analysis of data from the Sleep SAAF (Strong African American Families) RCT tests the effects of an RP intervention designed to prevent rapid infant weight gain on African American mothers’ infant feeding practices. Methods Primiparous African American mother-infant dyads (n = 194) were randomized to an RP or safety control intervention delivered by community research associates at infant age 3 and 8 weeks. At 16 weeks, mothers completed the Babies Need Feeding questionnaire, the Infant Feeding Styles Questionnaire, and the Babies Need Soothing questionnaire. Logistic regression and general linear models examined the effect of study group on infant feeding practices. Moderation analyses explored whether effects varied by feeding mode (any breast milk versus exclusive formula), maternal age (≥ 20 years versus Results RP mothers reported more responsive feeding (p = 0.005, partial η2 = 0.02), lower likelihood of using beverages other than breast milk/formula to soothe their infant (p = 0.01, OR = 0.42, 95% CI [0.2–0.8]), and less pressure with cereal than control mothers (p = 0.09, partial η2 = 0.02). RP mothers also reported less pressure to finish/soothe than controls (p = 0.007, partial η2 = 0.04); feeding mode (B = 0.74, p = 0.003) and maternal age (B = 0.53, p = 0.04) moderated this effect. There were no significant group differences in bottle-feeding practices (e.g., adding cereal to bottle, using an appropriate nipple/bottle size), or in context-based or emotion-based food to soothe. Conclusions Responsive parenting education influenced some feeding practices of African American mothers. Mothers reported using less pressure, a control-based feeding practice, and more responsive feeding than controls. Trial registration Sleep SAAF: A Strong African American Families Study. www.clinicaltrials.gov NCT03505203. Registered 3 April 2018.

The aim of this study was to evaluate the effect on bleeding risk when fluconazole is administered concomitantly with direct oral anticoagulants (DOACs).This was a retrospective cohort study including hospitalized adult patients prescribed a DOAC with or without fluconazole.The Ohio State University Wexner Medical Center, a tertiary care academic medical center with more than 1800 beds.Hospitalized patients ages 18-89 years who received apixaban or rivaroxaban with or without fluconazole from October 1, 2016, to September 30, 2021, were included. The minimum duration of DOAC or DOAC with fluconazole therapy was 48 h. Patients were excluded if they received fluconazole400 mg daily or a DOAC at doses outside those recommended for atrial fibrillation or venous thromboembolism treatment or prophylaxis. Patients were matched based on DOAC received.Patients who received a DOAC with fluconazole were compared with those receiving a DOAC alone. The primary outcome was a composite of major, clinically relevant nonmajor, and minor bleeding events at 30 days.There were 216 patients included, 108 in the DOAC with fluconazole group and 108 in the DOAC alone group. More patients in the DOAC with fluconazole group experienced bleeding at 30 days compared with the DOAC alone group [35/108 (32%) vs. 21/108 (19%), respectively; p = 0.03]; however, after adjusting for proven confounding variables (hemoglobin and concomitant carvedilol) this was found not to be statistically significant [adjusted odds ratio 1.71, 95% confidence interval 0.85-3.40].Patients receiving a DOAC with fluconazole were not at significantly increased risk for bleeding at 30 days compared with those receiving a DOAC alone after controlling for confounding variables. As an increasing number of patients are prescribed DOACs, the results of this study may inform clinical decision-making on the safety of concomitant DOAC and fluconazole use.

School meals are associated with improved nutrition and health for millions of US children, but school closures due to the COVID-19 pandemic disrupted children's access to school meals. Two policy approaches, the Pandemic Electronic Benefit Transfer (P-EBT) program, which provided the cash value of missed meals directly to families on debit-like cards to use for making food purchases, and the grab-and-go meals program, which offered prepared meals from school kitchens at community distribution points, were activated to replace missed meals for children from low-income families; however, the extent to which these programs reached those who needed them and the programs' costs were unknown.To assess the proportion of eligible youths who were reached by P-EBT and grab-and-go meals, the amount of meals or benefits received, and the cost to implement each program.This cross-sectional study was conducted from March to June 2020. The study population was all US youths younger than 19 years, including US youths aged 6 to 18 years who were eligible to receive free or reduced-price meals (primary analysis sample).Receipt of P-EBT or grab-and-go school meals.The main outcomes were the percentage of youths reached by P-EBT and grab-and-go school meals, mean benefit received per recipient, and mean cost, including implementation costs and time costs to families per meal distributed.Among 30 million youths eligible for free or reduced-price meals, grab-and-go meals reached an estimated 8.0 million (27%) and P-EBT reached 26.9 million (89%). The grab-and-go school meals program distributed 429 million meals per month in spring 2020, and the P-EBT program distributed $3.2 billion in monthly cash benefits, equivalent to 1.1 billion meals. Among those receiving benefits, the mean monthly benefit was larger for grab-and-go school meals ($148; range across states, $44-$176) compared with P-EBT ($110; range across states, $55-$114). Costs per meal delivered were lower for P-EBT ($6.46; range across states, $6.41-$6.79) compared with grab-and-go school meals ($8.07; range across states, $2.97-$15.27). The P-EBT program had lower public sector implementation costs but higher uncompensated time costs to families (eg, preparation time for meals) compared with grab-and-go school meals.In this economic evaluation, both the P-EBT and grab-and-go school meal programs supported youths' access to food in complementary ways when US schools were closed during the COVID-19 pandemic from March to June 2020.

Ultrasound screening for thyroid cancer is recommended in familial adenomatous polyposis (FAP). This study investigated the prevalence of thyroid neoplasia in children with FAP.Cross-sectional study of children with FAP at an academic hospital. Clinical and ultrasound data were analyzed for the prevalence of thyroid nodules and cancer.Of 37 children with FAP, 8 (22%) had thyroid nodules and 2 (5%) had thyroid cancer. Nodules (30%) and cancer (9%) were more common among female subjects and rare among male subjects.Thyroid ultrasound screening in adolescence may benefit female subjects with FAP but has limited utility in male subjects.

The health benefits of breast milk feeding have been well-established, yet disparities exist, with African American mothers having the lowest breast milk feeding rates in the United States. This prospective, longitudinal study examined infant feeding (breast milk and/or infant formula) from birth to age 16 weeks, predictors of any breast milk feeding by age 1 week, and predictors of cessation of any breast milk feeding by ages 3, 8, and 16 weeks among primiparous African American mothers. This secondary analysis included 185 mother–infant dyads from the Sleep SAAF (Strong African American Families) study, a randomized clinical trial testing a responsive parenting vs. child safety control intervention. Mothers reported sociodemographic and psychosocial characteristics at age 1 week and infant feeding practices at ages 1, 3, 8, and 16 weeks. Rates of any breast milk feeding decreased from 66.5% at 1 week to 23.3% at 16 weeks. Bivariate logistic regression models showed that prepregnancy BMI (OR = 1.09), working prepregnancy (OR = 2.25), and food insecurity (OR = 2.49) significantly increased the odds of mothers feeding any breast milk by 1 week, whereas Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation (OR = 0.21) significantly decreased the odds. Bivariate logistic regression models showed that Supplemental Nutrition Assistance Program (SNAP) participation (OR = 2.86) and racial discrimination (OR = 2.14) significantly increased the odds of cessation of any breast milk feeding by 3 weeks. SNAP (OR = 2.33) and WIC (OR = 2.38) participation significantly increased the odds of cessation of any breast milk feeding by 8 weeks, whereas higher prepregnancy BMI (OR = 0.95) decreased the odds. Higher mother’s age (OR = 0.92) significantly decreased the odds of cessation of any breast milk feeding by 16 weeks. The findings can be used to inform targeted interventions to promote mothers feeding any breast milk and help reduce breast milk feeding disparities among African American mothers.

The Society of Surgical Oncology collaborates with the National Resident Matching Program (NRMP) to facilitate the Complex General Surgical Oncology (CGSO) Match.The purpose of this study was to understand trends in CGSO Match outcomes. We hypothesized that (1) match rates would increase with time; (2) US allopathic graduates would have higher match rates than non-US allopathic graduates; and (3) most applicants would match at one of their top three ranked choices.The NRMP provided applicant and program data from the CGSO Match (2014-2021). Chi-square tests elucidated temporal trends and match rates by applicant archetype.The annual number of applicants decreased from 103 to 90 (13% decrease), while the annual number of fellowship positions increased from 56 to 67 (20% increase) from 2014-2021. The annual percentage of applicants who did not match decreased from 46% to 26% (p 0.05). Annual match rates increased from 54% to 74% (p 0.05). US allopathic graduates had higher match rates than non-US allopathic graduates but this disparity narrowed over time (84% vs. 55% in 2021; p 0.001). Approximately half of all applicants matched at one of their top three choices (first, 29%; second, 12%; third, 8%). Applicants matching at one of their top three choices increased from 36% to 50% (p 0.05).CGSO Match rates have increased over the past decade, thus primarily benefiting non-US allopathic graduates. Most applicants match at one of their top three choices. More research is needed to understand disparities in match rates by applicant and residency program characteristics.

A benzo[6]annulene, 4-(tert-butyl)-N-(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl) benzamide (1a), was identified as an inhibitor against Chikungunya virus (CHIKV) with antiviral activity EC(90) = 1.45 μM and viral titer reduction (VTR) of 2.5 log at 10 μM with no observed cytotoxicity (CC(50) = 169 μM) in normal human dermal fibroblast cells. Chemistry efforts to improve potency, efficacy, and drug-like properties of 1a resulted in a novel lead compound 8q, which possessed excellent cellular antiviral activity (EC(90) = 270 nM and VTR of 4.5 log at 10 μM) and improved liver microsomal stability. CHIKV resistance to an analog of 1a, compound 1c, tracked to a mutation in the nsP3 macrodomain. Further mechanism of action studies showed compounds working through inhibition of human dihydroorotate dehydrogenase in addition to CHIKV nsP3 macrodomain. Moderate efficacy was observed in an in vivo CHIKV challenge mouse model for compound 8q as viral replication was rescued from the pyrimidine salvage pathway.

OBJECTIVEInhibition of platelet aggregation is universally used to prevent thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Previously, the authors demonstrated that two different commercially available measures of adenosine diphosphate (ADP)–dependent platelet inhibition—the VerifyNow P2Y12 clopidogrel assay (measured in platelet reactivity units [PRU]) and maximal amplitude (MA) attributable to ADP activity (MA-ADP) derived from thromboelastography (TEG) with platelet mapping (PM)—yielded wildly different results. This study sought to analyze observed complications to quantify the ideal therapeutic windows for both tests.METHODSNinety-one patients with simultaneous or near-simultaneous PRU and TEG-PM results who underwent craniocervical endovascular stenting at the authors’ institution between September 2015 and November 2017 were identified and retrospectively enrolled. From November 2017 until June 2019, 109 additional patients were prospectively enrolled. For this study, in-hospital thrombotic and hemorrhagic complications (both CNS and non-CNS) were tabulated, and receiver operating characteristic (ROC) curve analysis was used to identify threshold values of the PRU and MA-ADP for predicting each type of complication.RESULTSOf the 200 patients enrolled, 7 were excluded because of anemia or thrombocytopenia outside of the test manufacturer’s specified ranges and 1 was excluded because they did not have a TEG-PM result. Including complications of all severities, there were a total of 15 CNS thrombotic complications, 1 access-site thrombotic complication, 3 CNS hemorrhages, 8 access-site hemorrhagic complications, and 3 hemorrhagic complications not affecting either the CNS or the access site. ROC curve analysis yielded therapeutic threshold values of 118–144 PRU. The results demonstrated PRU has a significant dose-dependent effect on the rates of thrombosis and hemorrhage. Logistic regression models did not demonstrate statistically significant relationships between the MA-ADP and either thrombosis or hemorrhage. ROC analysis based on these models is of little value and did not identify significant threshold values for MA-ADP.CONCLUSIONSThere continues to be poor correlation between the results of TEG-PM and PRU. PRU accurately predicted complications, with a relatively narrow ideal value range of 118–144. The MA-ADP alone does not appear able to accurately predict either hemorrhagic or thrombotic complications in this group.

Background The ACGME mandates that residency programs provide training related to high value care (HVC). The purpose of this study was to explore HVC education in general surgery residency programs. Methods An electronic survey was distributed to general surgery residents in geographically diverse programs. Results The response rate was 29% (181/619). Residents reported various HVC components in their curricula. Less than half felt HVC is very important for their future practice (44%) and only 15% felt confident they could lead a QI initiative in practice. Only 20% of residents reported participating in a root cause analysis and less than one-third of residents (30%) were frequently exposed to cost considerations. Conclusion Few residents feel prepared to lead quality improvement initiatives, have participated in patient safety processes, or are aware of patients’ costs of care. This underscores the need for improved scope and quality of HVC education and establishment of formal curricula.

Variability in working memory (WM) task selection likely contributes to heterogeneity in effect size estimates of deficiencies in youth with attention-deficit/hyperactivity disorder (ADHD). This has resulted in the development of brief, easy to administer assessments such as the NIH List Sorting Working Memory (LSWM) task from the NIH Cognitive Toolbox in hopes of standardizing measurement of this construct. Unfortunately, substantial questions persist regarding the specific constructs being evaluated by this task (e.g., visuospatial [VS] or phonological [PH] WM) as well as the ability of this task to detect WM deficits in previously identified impaired groups (e.g., ADHD). The current study examines the extent to which the LSWM task is associated with VS and PHWM performance as well as symptoms of ADHD. Additionally, we examined the magnitude of differences between ADHD and Typically Developing (TD) youth on this task relative to empirically derived WM tasks utilized in the past. Forty-six children (25 ADHD, 21 TD) completed multiple WM tasks. The LSWM task was moderately associated with PHWM and demonstrated relatively weaker associations with VSWM. Symptoms of inattention and hyperactivity/impulsivity were unrelated to the LSWM task; whereas tasks assessing PH and VSWM were moderately associated with inattention and weakly associated with hyperactivity (VSWM only). No significant between-group differences in performance emerged on the LSWM task; however, significant large-magnitude group differences were observed on both the PH and VSWM tasks. These findings suggest that the LSWM task may lack the ability to detect WM difficulties in youth with ADHD.

There is little evidence on the role of diet in childhood/adolescence and multiple sclerosis (MS) in adulthood. The MS Sunshine Study recruited adults with recent-onset MS ( n = 602) and matched controls ( n = 653). Of these, 84% provided dietary recall for specific ages between childhood and young adulthood (6–10, 11–15 and 16–20 years). We used logistic regression to test associations between age-specific diet and case-control status. Consumption of fruit (all ages), yoghurt (all ages) and legumes (11–15 years) was associated with lower probability of adult-onset MS (all p

The opioid crisis has continued to progress in the United States and the rest of the world. As this crisis continues, there is a pressing need for a rapid and cost-effective method for detecting fentanyl. Recent studies have suggested that lateral flow immunoassays (LFIs) could fill this technology gap. These qualitative paper-based assays contain antibodies designed to react with fentanyl and provide positive or negative results within a matter of minutes. In this study, two different LFI configurations for the detection of fentanyl were examined (dipsticks and cassettes) for effectiveness of detection using seized drug samples and postmortem urine samples. In the current study, 44 seized drug samples (32 fentanyl-positive, 12 fentanyl-negative) and 14 postmortem urine samples (10 fentanyl-positive, 4 fentanyl-negative) were analyzed. All 32 fentanyl-containing seized drug samples and 10 postmortem fentanyl-positive urine samples displayed positive LFI results with both LFI configurations. The fentanyl dipsticks displayed a sensitivity of 100%, a specificity of 75%, and an efficiency of 93.2% for seized drug samples and a sensitivity, specificity, and efficiency of 100% for postmortem urine. Analysis of the fentanyl cassettes displayed a sensitivity, specificity, and efficiency of 100% for seized drug samples and a sensitivity of 100%, a specificity of 75%, and an efficiency of 92.9% for postmortem urine samples. These data point to the utility of LFIs as a quick and low resource-dependent option for presumptive detection of fentanyl in real-world situations.

To identify evidence related to association between the nurse work environment and severe maternal morbidity in high-income countries.Quantitative Systematic review.Cumulative Index of Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, PubMed/Medline, and Scopus were systematically searched for studies published in English from January 1990-December 2019. Studies were selected based on a priori eligibility criteria.Two independent reviewers used a two-phase screening process. First, the reviewers assessed the eligibility of studies based on titles and abstracts; followed by assessing the full text of all remaining studies based on the eligibility criteria. An adapted version of the Joanna Briggs Institute data extraction tool was created to extract relevant information from studies reviewed during the second screening phase.Of the 535 de-duplicated articles examined by two independent reviewers, there were no eligible empirical studies that assessed the association between nurse work environment and severe maternal morbidity.There is a critical gap in knowledge regarding how characteristics of the nurse work environment may influence severe maternal morbidity in high-income countries. Future directions for nursing research include using available maternal health surveillance hospital-level data, conducting high-quality studies, and using evidence-based frameworks to guide future studies. Future directions for nursing practice include leveraging professional learning communities for nursing education and training and leveraging quality improvement initiatives.As the first known systematic review of its kind, this 'empty review' provides evidence of a lacking body of literature on the association between nurse work environment, as a modifiable organizational characteristic and preventable severe maternal morbidity in high-income countries. This article provides a call to action in the form of five recommendations for future nursing research and practice, which could serve to elucidate research, practice, and policy opportunities to reduce preventable severe maternal morbidity in high-income countries.目的: 确定高收入国家护士工作环境与严重孕产妇发病率之间关系的相关证据。 设计: 定量系统评估。 数据来源: 对护理学及医疗相关文献累计索引、Cochrane系统评估数据库、PubMed/Medline和Scopus中1990年1月至2019年12月期间以英文形式发表的研究进行了系统检索。根据先验的资格标准进行研究选择。 评估方法: 两名独立评估员采用了二阶段筛选过程。首先, 评估员根据标题和摘要评估研究的资格条件; 然后根据资格标准评估所有剩余研究的全文内容。创建了Joanna Briggs Institute数据提取工具的改编版, 以便从第二个筛选阶段审查的研究中提取相关信息。 结果: 在两名独立评估员审查的535篇去重文章中, 没有符合条件的实证研究评估护士工作环境与严重孕产妇发病率之间的关系。 结论: 在高收入国家, 关于护士工作环境的特点如何影响严重孕产妇发病率的问题, 目前存在关键知识空白。护理研究的未来方向包括利用现有的孕产妇健康监测医院层面的数据, 开展高质量的研究, 并利用循证框架来指导未来的研究。护理实践的未来方向包括利用专业学习社区进行护理教育和培训, 以及利用质量改进举措。 影响: 作为第一项已知的系统性评估,这种‘空洞的评估’提供了证据, 证明在高收入国家, 作为一种可改变的组织特征的护士工作环境与可预防的严重孕产妇发病率之间缺乏文献参考。本文以对未来护理研究和实践提出五项建议的形式发出行动呼吁, 这些建议可有助于阐明研究、实践和政策机会, 以降低高收入国家可预防的严重孕产妇发病率。.

This study was undertaken to evaluate a multicomponent health system intervention designed to reduce escalating disease-modifying treatment (DMT) expenditures and improve multiple sclerosis (MS) outcomes by increasing use of preferred formulary and highly effective DMTs (HETs).We conducted a trend study of treatment utilization and expenditure outcomes prior to (2009-2011) and during (2012-2018) MS Treatment Optimization Program (MSTOP) implementation in Kaiser Permanente Southern California (KPSC) compared to a Kaiser Permanente region of similar size. Annual relapse rates (ARRs) were obtained from KPSC's electronic health records.Adherence to preferred formulary DMTs increased from 25.4% in 2011 to 72.2% in 2017 following MSTOP implementation in KPSC and 22.1% to 43.8%, respectively, in the comparator. KPSC's annual DMT expenditures in 2018 were less than in 2011 despite an 11.3% increase in DMT-treated members. The decline in average per patient per year of treatment expenditures from a peak of $43.1 K in 2014 to $26.3 K in 2018 in KPSC was greater than the comparator, which peaked at $52.1 K and declined to $40.0 K in 2018. Over the 7 years following initiation of MSTOP, cumulative MS DMT expenditures were $161.6 million less than the comparator. HET use increased to 62.5% of per patient treatment-years versus 32.4% in the comparator. This corresponded to a 69% decline in adjusted ARR (95% confidence interval = 64.1-73.2%; p 0.0001) among DMT-treated patients in KPSC.A novel, expert-led health system intervention reduced MS DMT expenditures despite rising prices while simultaneously reducing MS relapse rates. Our focus on health system progress toward meaningful, measurable targets could serve as a model to improve quality and affordability of MS care in other settings. ANN NEUROL 2022;92:164-172.

Models of impaired social competence in autism spectrum disorder (ASD) highlight deficits in social cognition and social behavior. The Contextual Assessment of Social Skills (CASS) is a laboratory-based assessment of conversation ability in which participants interact with trained confederates who act interested (CASS-I) and bored (CASS-B), sequentially. The increased ecological validity of the CASS allows for better generalization to real-world social situations. Participants' perceptions of confederate behavior, assessed by the CASS Conversation Rating Scale (CRS), might offer additional utility as a metric of social cognition. The current study examined CASS confederate behavior (adherence to interested or bored condition) and both internal validity and convergent validity of the CASS as a measure of social behavior and social cognition. Fifty adolescents with ASD participated as part of a multisite randomized clinical trial. Adherence ratings were consistent across gender and site, with interested confederates significantly out-performing bored confederates. The ability to distinguish between interested and bored confederates was positively associated with CASS social behavior and social cognition tasks, although social behavior during the CASS was not consistently associated with parent-rated social behavior. Controlling for confederate behavior did not significantly alter these associations. Findings demonstrate strong internal validity of the CASS and, partially, external validity of the CASS as a measure of social cognition. Findings highlight nuanced differences in social behavior and social cognition. The CASS shows promise as an outcome measure for clinical interventions and should be incorporated into a multimethod battery to assess social competence in individuals with ASD. LAY SUMMARY: Social cognition and social behavior should be studied together to examine social competence in youth with autism. The Contextual Assessment of Social Skills (CASS), a behavioral observation measure, shows promise toward this end; findings suggest the CASS taps social cognition and social behavior when administered alongside a participant rating scale of their conversation partner's engagement. Continued research, including examination of the CASS, may inform best practices in comprehensive assessment of social competence in autism. Autism Res 2021, 14: 709-719. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Highlights • Targeted anti-cytokine agents, tocilizumab and anakinra, used to treat COVID-19 related cytokine storm yield mixed results. • Early identification of cytokine storm using laboratory abnormalities can detect patients prior to mechanical ventilation. • Early identification and treatment of cytokine storm with anakinra and corticosteroids led to improved outcomes compared to initiating tocilizumab shortly after mechanical ventilation. • Early identification and treatment of cytokine storm may be more important than which anti-inflammatory treatment is chosen. • Our results provide additional support for the use of corticosteroid treatment of COVID19 cytokine storm., Objective To examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS). Methods We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from the electronic health record. Results At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only 7 (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated). Patients who died had more severe sepsis and respiratory failure and met COVID-CS laboratory criteria longer (median = 3 days) compared to those extubated/never intubated (median = 1 day). After accounting for differences in disease severity at treatment initiation, this apparent superiority of anakinra over tocilizumab was no longer statistically significant (propensity score-adjusted hazards ratio 0.46, 95% confidence interval 0.18–1.20). Conclusions Prompt identification and treatment of COVID19-CS prior to intubation may be more important than the specific type of anti-inflammatory treatment. Randomized controlled trials of targeted anti-cytokine treatments and corticosteroids should report duration of cytokine storm in addition to clinical severity at randomization.

Interest in symptoms of sluggish cognitive tempo (SCT) has led to a number of studies evaluating how these symptoms respond to treatment commonly utilized in youths with symptoms of ADHD. No study to date, however, has examined the extent to which symptoms of SCT predict behavioral treatment response in youths across multiple domains of functioning. The current preliminary investigation integrates a number of methodological (e.g., direct observations) and analytic (e.g., Poisson regression) refinements to evaluate the extent to which symptoms of SCT predict treatment responses across multiple domains including behavioral (e.g., interruptions, rule violations), social (e.g., social skills, negative verbalizations), and severe behavioral difficulties (e.g., intentional aggression) above and beyond other demographic characteristics (e.g., symptom severity, Full Scale Intelligence Quotient [FSIQ]). A relatively small sample of 37 children, aged six to 12 years ( M = 8.03, SD = 1.83, 35 males: 2 females) attending an eight week multi-component intensive behavioral treatment program for youths with behavioral difficulties participated in the current study. Baseline parental perceptions of SCT were collected prior to the initiation of treatment. Results from this preliminary investigation revealed that pre-treatment SCT symptoms only predicted a less robust treatment response to time out which was associated also with parent’s perceptions of underlying working memory problems. Results revealed also that pre-treatment SCT symptoms failed to predict paraprofessional counselor’s and teacher’s improvement ratings of both rule following and social skills following treatment. Notably, other potential predictors (e.g., symptom severity, FSIQ) also largely failed to predict behavioral treatment response.

We examined whether Medicaid-enrolled women in CenteringPregnancy group prenatal care had higher rates of (1) postpartum visit attendance and (2) postpartum uptake of contraceptives, compared to women in individual prenatal care.We linked birth certificates and Medicaid claims for women receiving group prenatal care in 18 healthcare practices and applied preferential-within cluster propensity score methods to identify a comparison group, accounting for the nested data structure by practice. We examined five standardized, claims-based outcomes: postpartum visit attendance; contraception within 3 days; and any contraception, long-acting reversible contraception (LARC), and permanent contraception within eight weeks. We assessed outcomes using logistic regression for two treatment levels: (1) any group attendance compared to no group attendance and (2) attendance at five or more group sessions to at least five prenatal care visits, including crossovers attending fewer than five group sessions (minimum threshold analysis).Women attending at least five group sessions had higher rates of postpartum visit attendance (71.5% vs. 67.5%, p .05). Women with any group attendance (N = 2834) were more likely than women with individual care only (N = 13,088) to receive contraception within 3 days (19.8% vs. 16.9%, p .001) and to receive a LARC within eight weeks' postpartum (18.0% vs. 15.2%, p .001). At both treatment levels, group participants were less likely to elect permanent contraception (5.9% vs. 7.8%, p 0.001). Women meeting the five-visit group threshold were not more likely to initiate contraception or LARCs within 8 weeks' postpartum.Participation in at least five group compared to five individual prenatal care visits is associated with greater rates of postpartum visit attendance. Additional engagement and education in group prenatal care may influence postpartum visit attendance.Planning for postpartum care and contraception during prenatal care is an important strategy for connecting women to postpartum healthcare. Regardless of prenatal care model, women have low uptake of contraception in the postpartum period. Increased use of group prenatal care with its scheduled family planning discussion may help to increase postpartum contraceptive uptake. This benefit is dependent on availability of postpartum contraception options.

Background The literature includes multiple descriptions of successful nurse-led interventions, but the effects of nurse-led education on nurse and patient satisfaction in an executive health program are unknown. Local problem Nursing staff desire to practice more fully within their scope of licensure. Increased practice demands raised questions about whether nurse-led education would improve staff and patient satisfaction. Methods/interventions A structured quality improvement process was used to design a nurse-led patient education program. Pilot measures included 5-point Likert scale patient and staff satisfaction surveys. Nurse burnout was also measured before and after the pilot. Results Patient satisfaction was high; 96% reported favorable satisfaction during the pilot, with sustained results over the following 3 years. Nurses' sense of achievement improved by 12 percentage points, and perception of making good use of skills and abilities increased by 39 percentage points. Conclusions A nurse-led patient education intervention contributed to improved staff satisfaction while sustaining a positive patient experience.

Objectives: This community-based participatory research focused on physical and social barriers to healthcare for refugee women in Melbourne, Australia.Design: Women from non-English speaking backg...

To test whether an Internet-delivered cognitive behavioral therapy for insomnia (CBT-I) program for older adults attenuates symptoms of depression and anxiety.Adults aged ≥ 55 with insomnia were randomized to SHUTi-OASIS (Sleep Healthy Using the Internet for Older Adult Sufferers of Insomnia and Sleeplessness; N = 207) or Patient Education (PE; N = 104). Depression and anxiety were assessed (HADS-D and HADS-A, respectively) at baseline, post-assessment, and 6- and 12-month follow-ups.Multilevel modeling of HADS-D showed a condition by time interaction (F[3,779] = 3.23, p = .02): SHUTi-OASIS participants reported lower symptoms than PE at post-assessment. There was no such interaction effect for HADS-A (F[3,779] = 2.12, p = .10). Generalized linear modeling showed no moderation of effects by baseline symptom severity.Participants randomized to Internet-delivered CBT-I showed stable depression and anxiety across time, while control participants' depressive symptoms briefly increased. CBT-I may help prevent development or worsening of psychological distress among older adults with insomnia.[Registered at ClinicalTrials.gov; identifier removed for anonymity].

Objectives To assess whether head CT with 3D reconstruction can replace skull radiographs (SXR) in the imaging investigation of suspected physical abuse (SPA)/abusive head trauma (AHT). Methods PACS was interrogated for antemortem skeletal surveys performed for SPA, patients younger than 2 years, SXR and CT performed within 4 days of each other. Paired SXR and CT were independently reviewed. One reviewer analysed CT without and (3 months later) with 3D reconstructions. SXR and CT expert consensus review formed the gold standard. Observer reliability was calculated. Results A total of 104 SXR/CT examination pairs were identified, mean age 6.75 months (range 4 days to 2 years); 21 (20%) had skull fractures; two fractures on CT were missed on SXR. There were no fractures on SXR that were not seen on CT. For SXR and CT, respectively: PPV reviewer 1, 95% confidence interval (CI) 48–82% and 85–100%; reviewer 2, 67–98% and 82–100%; and NPV reviewer 1, 95%, CI 88–98% and 96–100%; reviewer 2, 88–97% and 88–98%. Inter- and intra-observer reliability were respectively the following: SXR, excellent (kappa = 0.831) and good (kappa = 0.694); CT, excellent (kappa = 0.831) and perfect (kappa = 1). All results were statistically significant (p Conclusions CT has greater diagnostic accuracy than SXR in detecting skull fractures which is increased on concurrent review of 3D reconstructions and should be performed in every case of SPA/AHT. SXR does not add further diagnostic information and can be omitted from the skeletal survey when CT with 3D reconstruction is going to be, or has been, performed. Key Points • Head CT with 3D reconstruction is more sensitive and specific for the diagnosis of skull fractures. • Skull radiographs can be safely omitted from the initial skeletal survey performed for suspected physical abuse when head CT with 3D reconstruction is going to be, or has been, performed.

Hypoalbuminemia is common among individuals with obesity who qualify for bariatric surgery, but its relevance to clinical outcomes after bariatric surgery remains to be established.To examine the association of preoperative serum albumin with 30-day postoperative outcomes.Data from the 2015-2019 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use Files were used.Preoperative serum albumin level was categorized as hypoalbuminemia (3.5 g/dL), and normoalbuminemia (3.5-5.5 g/dL) among patients who underwent bariatric surgery. Multivariate logistic regression models were used to determine the association of preoperative hypoalbuminemia with 30-day postoperative mortality and other co-morbid outcomes.Among 633,011 adult patients, 85.1% were women and the mean (standard deviation) age was 44.8 (12.0) years. The prevalence of hypoalbuminemia was 6.13% (n = 38,792). After adjustment for procedure type and demographic, lifestyle, and co-morbidity covariates, the odds ratio (OR) (95% confidence interval [CI]) for mortality was 1.42 (1.10, 1.82) for hypoalbuminemia. For all other outcomes, the ORs (95% CIs) for hypoalbuminemia ranged from 1.03 (.67-1.60) for cardiac arrest requiring CPR to 2.32 (1.66-3.25) for failure to be discharged by day 30. The ORs for several associations were higher for severe hypoalbuminemia than marginal hypoalbuminemia.Preoperative hypoalbuminemia was associated with several negative 30-day postoperative bariatric surgery outcomes and tended to be worse for severe hypoalbuminemia compared with marginal hypoalbuminemia. These findings suggest that serum albumin may be a useful biomarker to screen for negative bariatric surgery outcomes.

Thyroid nodules with atypia of undetermined significance (AUS) are challenging to manage because of their intermediate risk of malignancy. Subclassification of atypia can refine malignancy risk in adult AUS nodules but has not been evaluated in children.This was a retrospective cohort study of pediatric patients (19 years old) who underwent fine-needle aspiration (FNA) of a thyroid nodule with resulting AUS cytology. Atypia was subclassified as nuclear only, architectural only, nuclear and architectural, or oncocytic. The primary outcome was the association between atypia subtype and malignancy. A secondary outcome was the association of atypia subtype with repeat FNA cytology.Sixty-eight AUS nodules in 61 patients were analyzed. The median age at FNA was 16.2 years (range, 9.8-18.9 years). Twenty-four nodules (35%) were malignant. Nuclear atypia only was present in 17 nodules (25%), architectural atypia only was present in 27 nodules (40%), nuclear and architectural atypia was present in 20 nodules (29%), and predominantly oncocytic features were present in 4 nodules (6%). The presence of nuclear atypia was associated with a significantly increased rate of malignancy (22 of 37 [59%] vs 2 of 31 [6.5%]; P.001), whereas architectural atypia was not associated with malignancy (P = .8). Repeat FNA was performed in 42 of 68 nodules (62%). In nodules with initial nuclear and architectural atypia, benign repeat cytology had a high false-negative rate (3 of 6; 50%).Pediatric AUS nodules with nuclear atypia have a high rate of malignancy, but architectural atypia is not associated with malignancy. In nodules with nuclear atypia, repeat FNA may inform clinical decisions regarding the need for resection. In the absence of suspicious clinical features, nodules without nuclear atypia might be considered for observation rather than resection or repeat FNA.

ImportanceRituximab and other B-cell–depleting therapies blunt humoral responses to SARS-CoV-2 vaccines, particularly when the vaccine is administered within 6 months of an infusion. Whether this translates into an increased risk of hospitalization or death from COVID-19 is unclear.ObjectivesTo examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2–vaccinated persons with multiple sclerosis (MS) and whether delaying vaccination more than 6 months after rituximab treatment is associated with decreased risk.Design, Setting, and ParticipantsThis retrospective cohort study used Kaiser Permanente Southern California’s electronic health record to identify individuals from January 1, 2020, to February 15, 2022, who had MS and who had been vaccinated against SARS-CoV-2.ExposuresRituximab treatment compared with disease-modifying therapies (DMTs) that do not interfere with vaccine efficacy or being untreated (no or other DMT group). Among rituximab-treated patients, the exposure was receiving at least 1 vaccine dose more than 6 months after their last infusion compared with receiving all vaccine doses 6 months or less since their last infusion.Main Outcomes and MeasuresThe main outcome was hospitalization due to COVID-19 infection. The odds of infection resulting in hospitalization following SARS-CoV-2 vaccination were adjusted for race and ethnicity, advanced MS-related disability; vaccine type; booster dose; and, among rituximab-treated only analyses, cumulative rituximab dose and dose at last infusion. Exposures, outcomes, and covariates were collected from the electronic health record.ResultsAmong 3974 SARS-CoV-2–vaccinated people with MS (mean [SD] age, 55.3 [15] years; 2982 [75.0%] female; 103 [2.6%] Asian or Pacific Islander; 634 [16.0%] Black; 953 [24.0%] Hispanic; 2269 [57.1%] White; and 15 [0.3%] other race or ethnicity), rituximab-treated patients (n = 1516) were more likely to be hospitalized (n = 27) but not die (n = 0) compared with the 2458 individuals with MS receiving no or other DMTs (n = 7 and n = 0, respectively; adjusted odds ratio [aOR] for hospitalization, 7.33; 95% CI, 3.05-17.63). Receiving messenger RNA (mRNA) SARS-CoV-2 vaccine (aOR, 0.36; 95% CI, 0.15-0.90; P = .03) and receiving a booster vaccination (aOR, 0.31; 95% CI, 0.15-0.64; P = .002) were independently associated with a decreased risk of hospitalization for COVID-19. Among vaccinated rituximab-treated individuals with MS, receiving any vaccination dose more than 6 months after the last rituximab infusion was associated with a reduced risk of COVID-19 hospitalization (aOR, 0.22; 95% CI, 0.10-0.49).Conclusions and RelevanceThis cohort study’s findings suggest that rituximab-treated people with MS should be strongly encouraged to receive mRNA SARS-CoV-2 vaccines and boosters more than 6 months after their last rituximab infusion whenever possible. The low absolute risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS should not preclude use of rituximab, which has marked efficacy, cost, and convenience advantages over other DMTs.

To provide a stepwise guide to performing vNOTES hysterectomy, adnexectomy, and vault suspension, using 2 access platform methods.Narrated surgical video based on 2 cases of vNOTES for abnormal uterine bleeding and endometrial intraepithelial neoplasia.A single tertiary-care academic center.Step-by-step walk-through is shown to demonstrate the successful completion of a hysterectomy, adnexectomy, and vault suspension. Use of a traditional glove platform and that of an advanced access system, the GelPOINT Access System (Applied Medical), are illustrated. The surgical steps are summarized as follows: (1) colpotomy and abdominal entry, (2) transection of the uterosacral ligaments, (3) placement of an access platform, (4) upper abdominal survey, (5) transection of the uterine and cornual pedicles, (6) identification of the ureters, (7) bilateral salpingo-oophorectomy, (8) uterosacral ligament suspension, (9) cystoscopy, and (10) vaginal vault closure and tying of the suspension sutures.This video demonstrates the steps to safely reproduce a vNOTES hysterectomy, adnexectomy, and uterosacral ligament suspension with 2 access techniques. vNOTES offers scar-free surgery, improved access to high pedicles and surgical fields, and a favorable recovery profile, making it an attractive surgical route in appropriate candidates.

Background and ObjectivesThe goal of this work was to determine whether the prevalence of multiple sclerosis (MS) varies by race and ethnicity.MethodsWe conducted a retrospective cohort study of >2.6 million adults from the multiethnic, community-dwelling members of Kaiser Permanente Southern California. The complete electronic health records of individuals with at least 1 ICD-9 code for MS between January 1, 2008 and December 31, 2010 were reviewed. MS prevalence and 95% CIs stratified by age, sex, and race and ethnicity among 2010 members were estimated with binomial regression. Age- and sex-standardized prevalence was estimated according to the 2010 US Census population.ResultsWe identified 3,863 patients with MS. The average age of patients with prevalent MS was 51.7 years (SD 13.1 years), and 76.8% were women. The female preponderance was more pronounced among Black (81.2%) and Asian (83.6%) than White (76.3%) or Hispanic (74.5%) individuals with MS. Age- and sex-standardized MS prevalence per 100,000 was similarly high among Black (225.8, 95% CI 207.1–244.5) and White (237.7, 95% CI 228.2–247.2) and significantly lower among Hispanic (69.9, 95% CI 64.4–75.5) and Asian (22.6, 95% CI 17.1–28.1) persons. MS prevalence was highest between the ages of 35 and 64 years and declined after 65 years of age across all racial and ethnic groups. Among adults 18 to 24 years of age, the crude MS prevalence was low but was highest among Black and Hispanic young adults, lower in White people, and lowest in Asian/Pacific Islander individuals (48.5, 25.0, 18.0, and 7.1 per 100,000, respectively).DiscussionMS prevalence varies by race and ethnicity, being similarly high in White and Black and significantly lower in Hispanic and Asian persons in Southern California. Taken together with previous studies, these findings indicate that the burden of MS in the US Black community has long been underrecognized. More studies are needed to determine whether MS is an emerging disease among US Hispanic adults and whether MS susceptibility and prevalence vary among Hispanic or Asian individuals from different cultures or ancestral backgrounds.

There is a prominent "treatment gap" in relation to at-risk drinking (ARD), whereby a minority of at-risk drinkers ever access treatment. Research suggests that recognition of problem drinking is a necessary precursor for help-seeking and treatment.This systematic review and meta-analysis aimed to estimate the prevalence of ARD recognition within those meeting criteria for ARD.PsycINFO, Web of Science, Scopus, and MEDLINE were searched using the terms: problem* AND (recogni* OR perceive* OR perception OR self-identif*) AND alcohol - to identify studies published in English between 2000 and 2022. Studies reported the frequency (weighted or unweighted) of participants meeting ARD criteria that also directly identified ARD, perceived a need for help, or endorsed a readiness to change. The prevalence of ARD recognition was estimated using a random-effects meta-analysis with 95% confidence intervals (CIs).17 studies were included which provided data for 33,349 participants with ARD. Most (n = 14) were US studies. ARD was self-identified via a single indicator in 7 studies, whereas recognition was assessed via stages of change in 4 studies and need for help in 6 studies. The pooled prevalence of ARD recognition was 31% (95% CI: 25%-36%), and subgroup analyses indicated alcohol use severity, measure of recognition, and population type to be significant sources of heterogeneity.Most individuals with ARD fail to recognise their drinking problem so preventive approaches that promote recognition may be helpful. However, we must be cautious of how inconsistency in question framing affects self-reported problem recognition.

Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown.Patients with metastatic melanoma treated with chemotherapy after progression on immunotherapy with checkpoint inhibitors were identified retrospectively from 24 melanoma centres. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety were examined.In total, 463 patients were treated between 2007 and 2017. Fifty-six per cent had received PD-1-based therapy before chemotherapy. Chemotherapy regimens included carboplatin + paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes (9%, nab-paclitaxel 4%), fotemustine (6%) and others (13%). Median duration of therapy was 7.9 weeks (0-108). Responses included 0.4% complete response (CR), 12% partial response (PR), 21% stable disease (SD) and 67% progressive disease (PD). Median PFS was 2.6 months (2.2, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3), respectively. Twelve-month PFS was 12% (95% CI 2-15%). In patients who had received anti-PD-1 before chemotherapy, the ORR was 11%, and median PFS was 2.5 months (2.1, 2.8). The highest activity was achieved with single-agent taxanes (N = 40), with ORR 25% and median PFS 3.9 months (2.1, 6.2). Median OS from chemotherapy start was 7.1 months (6.5, 8.0). Subsequent treatment with checkpoint inhibitors achieved a response rate of 16% with a median PFS of 19.1 months (2.0-43.1 months). No unexpected toxicities were observed.Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between regimens. Chemotherapy has a limited role in the management of metastatic melanoma.

Background Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. Methods Fusion sarcomas (2020–2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). Results Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). Conclusions Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

The primary objectives were to determine the prevalence of and identify variables associated with respiratory bacterial co-infection in COVID-19 inpatients. Secondary outcomes included length of stay and in-hospital mortality. Eighty-two (11.2%) of 735 COVID-19 inpatients had respiratory bacterial co-infection. Fifty-seven patients met inclusion criteria and were matched to three patients lacking co-infection (N = 228 patients). Patients with co-infection were more likely to receive antibiotics [57 (100%) vs. 130 (76%), p < 0.0001] and for a longer duration [19 (13-33) vs. 8 (4-13) days, p

Access to fast and reliable nucleic acid testing continues to play a key role in controlling the COVID-19 pandemic, especially in the context of increased vaccine break-through risks due to new variants. We report a rapid, low-cost (~ 2 USD), simple-to-use nucleic acid test kit for self-administered at-home testing without lab instrumentation. The entire sample-to-answer workflow takes

Background:The role of omega-3 fatty acid in multiple sclerosis (MS) susceptibility is unclear.Objective:To determine whether fish/seafood intake or genetic factors that regulate omega-3 fatty acids levels are associated with MS risk.Methods:We examined the association of fish and shrimp consumption and 13 tag single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2 with risk of MS in 1153 individuals from the MS Sunshine Study, a case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California.Results:Consuming fish/seafood at least once a week or at least once a month with regular fish oil use was associated with 44% reduced odds of MS/CIS (adjusted OR = 0.56; 95% CI = 0.41–0.76; p = 0.0002) compared with consuming fish/seafood less than once a month and no fish oil supplementation. Two FADS2 SNPs (rs174611 and rs174618) were independently associated with a lower risk of MS (adjusted ORs = 0.74, 0.79, p = 0.0056, 0.0090, respectively). Association of FADS2 SNPs with MS risk was confirmed in an independent dataset.Conclusion:These findings suggest that omega-3 fatty acid intake may be an important modifiable risk factor for MS. This is consistent with the other known health benefits of fish consumption and complementary genetic studies supporting a key role for omega-3 regulation.

Objective Limited examples exist globally of coordinated, organisation-wide health literacy approaches to systematically improve the understandability and actionability of patient health information. Even fewer have been formally evaluated. The aim of this study was to use the Patient Education Materials Assessment Tool (PEMAT) to evaluate the effectiveness of an organisation-wide, evidence-based approach to improve the understandability and actionability of patient information materials in regional health service in New South Wales, Australia. Methods Two independent raters (blinded to the document version) evaluated pre- and post-implementation versions of 50 randomly-selected patient information materials using the PEMAT, with differences in understandability and actionability analysed using paired samples tests. Results Mean (±SD) overall scores for understandability increased significantly by 5% (95% CI 2–8; p = 0.002) up to 77%±10%, and mean actionability (±SD) increased significantly by 4% (95% CI 0–8; p = 0.046) up to 56%±22%. Conclusion These results demonstrate that organisation-wide approaches with standardised processes for staff to prepare, review and store written patient information and education materials can be successfully implemented to address the impacts and risks of low health literacy. Practice implications The success of this approach provides a framework for other health organisations to work in partnership with patients to make health information more understandable and actionable.

IntroductionBrain metastases are a significant source of morbidity and mortality for patients with lung cancer. Lung cancer can induce local and systemic immunosuppression, promoting tumor growth and dissemination. One mechanism of immunosuppression is tumor-induced expansion of programmed death-ligand 1 (PD-L1) expressing myeloid cells. Here, we investigate peripheral blood immune phenotype in NSCLC patients with or without brain metastasis.MethodsPeripheral blood was collected from patients with lung metastatic brain tumors and pre-metastatic lung cancer. Immunosuppressive monocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were quantified through flow cytometry. T cell reactivity was analyzed via ELISpot. Brain metastasis conditioned media was collected from tumor-derived cell cultures and analyzed for cytokines by ELISA. Naïve monocytes were stimulated with brain metastasis conditioned media to evaluate PD-L1 stimulation.ResultsPatients with brain metastatic lung carcinoma demonstrated increased peripheral monocyte PD-L1, MDSC abundance, and Treg percentage compared to early stage pre-metastatic patients and healthy controls. Patients with elevated peripheral monocyte PD-L1 had less reactive T cells and worse survival. Brain metastasis conditioned media stimulation increased monocyte PD-L1, and conditioned media IL-6 levels correlated with PD-L1 induction. Treatment with anti-IL-6 or anti-IL-6 receptor antibodies reduced PD-L1 expression. In summary, patients with lung cancer and brain metastases exhibit multiple markers of peripheral immunosuppression.ConclusionsThe frequency of PD-L1+ myeloid cells correlated with the presence of brain metastases.Tumor-derived IL-6 was capable of inducing PD-L1+ myeloid cellsin vitro, suggesting thatmonitoring of immunosuppressive factors in peripheral blood may identify new targets for therapeutic intervention in selected patients.

ZIKV infection during pregnancy causes microcephaly, but not all neonates are affected. This study shows that features of the maternal antibodies correlate with the risk of ZIKV-associated microcephaly., Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

The Roux-en-Y gastric bypass (RYGB) isuery ID="Q1" Text="Author:Kindly check the edit made in the article title." -->the most efficacious procedure of choice for obese patients with gastroesophageal reflux disease (GERD). The laparoscopic sleeve gastrectomy (LSG) has high rates of worsening GERD post operatively. Little evidence exists as to whether the use of objective foregut investigations has a meaningful impact on surgical procedure selection. This study examined whether a standard preoperative foregut evaluation protocol effected procedure selection in bariatric patients presenting for surgical evaluation with subjective symptoms of GERD. Patients presenting for bariatric surgery evaluation with subjective symptoms of GERD entered into a predetermined protocol of foregut evaluation. Patients initially underwent upper endoscopy and esophagram. If the patient desired a LSG, further testing with esophageal pH testing and high-resolution manometry was ordered. If significant pathology was discovered on any of these investigations RYGB was recommended, if investigations were normal LSG was felt to be permissible. Data were collected prospectively from July 2016 to December 2018 and reviewed. One hundred and thirty-three patients were identified as being eligible to have progressed through the protocol. Pathology was commonly discovered on preoperative evaluations. On EGD Barrett’s esophagus was discovered in 4%, grade C or D esophagitis in 18% and hiatal hernia in 36% of patients. On esophagram, hiatal hernia was discovered in 42.3% of patients. Abnormal esophageal motility was discovered in 41% and abnormal DeMeester scores in 83% of tested patients. Of the 133 patients evaluated, the final procedure the patient ultimately underwent was primarily determined based on protocol test results in 24.8% of cases. Foregut pathology is common in bariatric patients with subjective symptoms of GERD. Implementing a comprehensive protocol to objectively assess these patients leads to a significant clinical impact on which procedure these patients ultimately undergo.

Survival outcomes for patients with glioblastoma (GBM) are universally poor with only a small percentage of patients surviving five years beyond initial diagnosis. Activation of the immune system against tumor cells is the basis of immunotherapy and aims to facilitate long-term immune surveillance and tumor suppression. Cytomegalovirus (CMV) has emerged as an immunologic target in GBM given that tumor cells have been shown to express the CMV-associated proteins IE1 and pp65. Moreover, vaccine therapy targeting CMV antigens has promoted improved survival outcomes with long-term survivors. In this report, we present the case of a 69 year-old woman with GBM who survived seven years post-diagnosis. Following tumor resection, the patient underwent concomitant radiation and temozolomide therapy that was complicated by CMV colitis and abdominal abscesses. Despite not receiving adjuvant temozolomide, the patient demonstrated a five year progression-free survival before requiring re-resection for radiation necrosis. Following re-resection, the patient survived for two additional years. As the patient's tumor stained positive for CMV antigens IE1 and pp65, it is hypothesized that she developed an immune response against CMV during recovery that contributed to anti-tumor surveillance and prolonged survival. Overall, this case supports further investigation into the role of CMV and immunotherapy in GBM.