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Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers. CC BY 4.0Correspondence Address: Silventoinen, K.; University of Helsinki, P.O. Box 18, Finland; email: karri.silventoinen@helsinki.fi© 2021 The Authors

Background The Spontaneously Hypertensive Rat (SHR) Colony was established in 1963 and is the most commonly used rodent model for studying heart failure (HF). Ideally, animal models should recapitulate the clinical disease as closely as possible. Any drift in a genetic model may create a new model that no longer adequately represents the human pathology. Further, instability overtime may lead to conflicting data between laboratories and/or irreproducible results. While systolic blood pressure (SBP) is closely monitored during inbreeding, the sequelae of HF (e.g., cardiac hypertrophy) are not. Thus, the object of this review was to investigate whether the hypertension-induced sequelae of HF in the SHR have remained stable after decades of inbreeding. Methods A systematic review was performed to evaluate indices of cardiovascular health in the SHR over the past 60 years. For post hoc statistical analyses, studies were separated into 2 cohorts: Initial (mid to late 1900s) and Current (early 2000s to present) Colony SHRs. Wistar-Kyoto rats (WKY) were used as controls. Results SBP was consistent between Initial and Current Colony SHRs. However, Current Colony SHRs presented with increased concentric hypertrophy (i.e., elevated heart weight and posterior wall thickness) while cardiac output remained consistent. Since these changes were not observed in the WKY controls, cardiac-derived changes in Current Colony SHRs were unlikely due to differences in environmental conditions. Conclusions Together, these data firmly establish a cardiac-based phenotypic shift in the SHR model and provide important insights into the beneficial function of concentric hypertrophy in hypertension-induced HF.

Journalism stakeholders increasingly believe that they need to better understand the news audience to accomplish their goals. Our study explores the extent to which this “audience turn” has unfolded in the education of future journalists. Drawing on data collected from course syllabi from leading journalism schools throughout the United States, we find that few journalism courses include aspects focused on news audiences. Those that include readings and/or assignments relating to news audiences maintain a narrow focus on audience metrics. We conclude by discussing what these trends mean for the future of journalism and the audience gap in journalism education.

[Image: see text] The mu opioid receptor antagonist naloxone has been a vital, long-standing countermeasure in the ongoing battle against opioid use disorders (OUD) and toxicity. However, due to its distinctive short elimination half-life, naloxone has shown diminished efficacy in cases of synthetic opioid poisoning as larger or repeated doses of the antidote have been required to achieve adequate reversal of severe respiratory depression and prevent episodes of renarcotization. This report describes the synthesis, characterization, and in vivo evaluation of a novel, nanoparticle-based naloxone formulation that provides extended protection against the toxic effects of the powerful synthetic opioid fentanyl. The strategy was predicated on a modified two-step protocol involving the synthesis and subsequent nanoprecipitation of a poly(lactic-co-glycolic acid) polymer scaffold bearing a covalently linked naloxone chain end (drug loading ∼7% w/w). Pharmacokinetic evaluation of the resulting covalently loaded naloxone nanoparticles (cNLX-NP) revealed an elimination half-life that was 34 times longer than high dose free naloxone (10 mg/kg) in male Sprague–Dawley rats. This enhancement was further demonstrated by cNLX-NP in subsequent in vivo studies affording protection against fentanyl-induced respiratory depression and antinociception for up to 48 h following a single intramuscular injection. These discoveries support further investigation of cNLX-NP as a potential therapeutic to reverse overdose and prevent renarcotization from fentanyl and its potent analogs.

The term “innovation” carries a large burden in journalism. It has been weighted with both the promise and expectation that new technologies, actors and practices might finally be the solution to t...

Acute kidney injury (AKI) that improves in the pediatric intensive care unit (PICU) is associated with better outcomes compared to AKI that persists, but no study has investigated whether this also occurs in children undergoing cardiopulmonary bypass (CPB). A retrospective study of children ≤18 years who underwent CPB in three children’s hospitals was conducted. Patients were classified into groups by kidney recovery after AKI according to Acute Disease Quality Initiative (ADQI) guidelines. Adjusted regression models evaluated associations between kidney recovery group and hospital outcomes. Among 3620 children, AKI developed in 701 (19.4%): 610 transient AKI, 47 persistent AKI, and 44 acute kidney disease (AKD). Mortality increased with severity of kidney recovery group: 4.5% in the never developed AKI group, 8.9% in the transient AKI group, 25.5% in the persistent AKI group, and 31.8% in the AKD group (p

The accuracy of preoperative patient-reported weight was never evaluated in patients undergoing lower extremity procedures. The purpose of this study was to: (1) compare the disparity between patient-reported and measured weights in patients undergoing lower extremity total joint arthroplasty (LE-TJA) and arthroscopy; and (2) investigate the association between patient-specific factors (patient age, BMI, zip code, and psychiatric comorbidities) and the accuracy of patient-reported weight. Preoperative self-reported weights were retrospectively compared to measured weights in 400 LE-TJA and 85 control arthroscopy patients. The difference between reported and measured weights was calculated. Additionally, the percent of accurate reporting within 0.5, 1, and 5 kg ranges of the measured weight was calculated. Outcomes were compared between surgical modalities as well as between patient-specific factors. There was low disparity (p = 0.838) between patient-reported and measured weights among LE-TJA (mean difference 0.18 ± 3.63 kg; p = 0.446) and that of arthroscopy (0.27 ± 4.08 kg; p = 0.129) patients. Additionally, LE-TJA patients were equally likely to report weights accurately within 0.5 kg of the measured weight (74% vs. 71.76%; p = 0.908). LE-TJA and arthroscopy patients had similar reporting accuracy within 1 and 5 kg of the measured weights (p > 0.05). Preoperative patient-reported weights demonstrated acceptable accuracy in both LE-TJA and lower extremity arthroscopic orthopaedic patient populations making it a potentially reliable parameter of preoperative assessment.

Purpose To determine the positive predictive values (PPVs) of ICD-9, ICD-10, and Current Procedural Terminology (CPT)-based diagnostic coding algorithms to identify prosthetic joint infection (PJI) following knee arthroplasty (TKA) within the United States Veterans Health Administration. Methods We identified patients with: 1) hospital discharge ICD-9 or ICD-10 diagnosis of PJI, 2) ICD-9, ICD-10, or CPT procedure code for TKA prior to PJI diagnosis, 3) CPT code for knee X-ray within ±90 days of the PJI diagnosis, and 4) at least 1 CPT code for arthrocentesis, arthrotomy, blood culture, or microbiologic procedure within ±90 days of the PJI diagnosis date. Separate samples of patients identified with the ICD-9 and ICD-10-based PJI diagnoses were obtained, stratified by TKA procedure volume at each medical center. Medical records of sampled patients were reviewed by infectious disease clinicians to adjudicate PJI events. The PPV (95% confidence interval [CI]) for the ICD-9 and ICD-10 PJI algorithms were calculated. Results Among a sample of 80 patients meeting the ICD-9 PJI algorithm, 60 (PPV 75.0 %, [CI 64.1-84.0%]) had confirmed PJI. Among 80 patients who met the ICD-10 PJI algorithm, 68 (PPV 85.0%, [CI 75.3-92.0%]) had a confirmed diagnosis. Conclusions An algorithm consisting of an ICD-9 or ICD-10 PJI diagnosis following a TKA code combined with CPT codes for a knee X-ray and either a relevant surgical procedure or microbiologic culture yielded a PPV of 75.0% (ICD-9) and 85.0% (ICD-10), for confirmed PJI events and could be considered for use in future pharmacoepidemiologic studies. This article is protected by copyright. All rights reserved.

A new low-dose, once-a-week contraceptive transdermal delivery system (TDS) with 2.3-mg ethinyl estradiol (EE) and 2.6-mg levonorgestrel (LNG; Twirla®) has recently been approved by the US FDA for contraception of women with BMI 2. The rationale for developing this new patch, the preclinical study results and the results from two innovative Phase III clinical trials demonstrate that this patch has an acceptable Pearl index (4.3%) for its indicated users and has safety and tolerability comparable to other similar dose oral combined hormonal contraceptives. This new TDS provides an improvement over the existing TDS products, with significantly lower steady-state estrogen exposure, a level equal to that with 30-µg EE containing oral contraceptives.

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B1), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B2, B6, B12, and E. Impact Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

In the Dark and Stormy Archives (DSA) project, we focus on storytelling techniques to summarize collections of archived web pages. Since collections can have hundreds or even thousands of seeds (initial URLs) and each seed can be recrawled many times, with each version separately maintained, techniques that include information about all members of the collection can be overwhelming. The premise of storytelling is to focus on sampling exemplar pages from the collection, and present them in a social media interface familiar to users. We present Hypercane , the tool in the DSA suite responsible for selecting exemplar pages. Hypercane offers eight action statements that can be combined in various ways to customize the sample that is produced. Because of its modular design, Hypercane can also be used to analyze large web archive collections outside of the DSA suite.

Background We present a rare case of pregnancy and invasive placentation in a unruptured, noncommunicating rudimentary uterine horn at 20 weeks’ gestation. Case The patient was followed with ultrasound throughout early pregnancy and initial imaging for dating purposes showed a pregnancy within a communicating right horn of the uterus. At the 18-week anatomy ultrasound, the pregnancy was discovered to be within the noncommunicating, rudimentary left horn of the uterus. This was confirmed using pelvic magnetic resonance imaging. The patient opted for surgical management and subsequently underwent laparotomy and removal of the noncommunicating uterine horn and pregnancy. Placental tissue was adherent to the level of the serosa during surgery and pathologic diagnosis was significant for a placenta increta. Summary and Conclusion The patient recovered well from surgery and subsequently went on to have a successful term pregnancy delivered via cesarean section for breech in the right horn 15 months later.

Providers of total hip and knee replacements are being judged regarding quality/cost by payers using competition-based performance measures with poor medical and no socioeconomic risk adjustment. Providers might assume that other providers shed risk and the perception of added risk can influence practice. A poll was collected to examine such perceptions.In 2019 a poll was sent to the 2800 surgeon members of the American Association of Hip and Knee Surgeons using Survey Monkey while protecting respondent anonymity/confidentiality. The questions asked whether the perception of poorly risk-adjusted medical comorbidities and socioeconomic risk factors influence surgeons to selectively offer surgery.There were 474 surgeon responses. Prior to elective total hip arthroplasty/total knee arthroplasty, 95% address modifiable risk factors; 52% require a body mass index40, 64% smoking cessation, 96% an adequate hemoglobin A1C; 82% check nutrition; and 63% expect control of alcohol 2. Due to lack of socioeconomic risk adjustment, 83% reported feeling pressure to avoid/restrict access to patients with limited social support, specifically the following: Medicaid/underinsured, 81%; African Americans, 29%; Hispanics/ethnicities, 27%; and low socioeconomic status, 73%. Of the respondents, 93% predicted increased access to care with more appropriate risk adjustment.Competition-based quality/cost performance measures influence surgeons to focus on medical risk factors in offering lower extremity arthroplasty. The lack of socioeconomic risk adjustment leads to perceptions of added risk from such factors as well. This leads to marginal loss of access for patients within certain medical and socioeconomic classes, contributing to existing healthcare disparities. This represents an unintended consequence of competition-based performance measures.

Wastewater-based epidemiology is an emerging tool to monitor COVID-19 infection levels by measuring the concentration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater. There remains a need to improve wastewater RNA extraction methods’ sensitivity, speed, and reduce reliance on often expensive commercial reagents to make wastewater-based epidemiology more accessible. We present a kit-free wastewater RNA extraction method, titled “Sewage, Salt, Silica and SARS-CoV-2” (4S), that employs the abundant and affordable reagents sodium chloride (NaCl), ethanol and silica RNA capture matrices to recover 6-fold more SARS-CoV-2 RNA from wastewater than an existing ultrafiltration-based method. The 4S method concurrently recovered pepper mild mottle virus (PMMoV) and human 18S ribosomal subunit rRNA, both suitable as fecal concentration controls. The SARS-CoV-2 RNA concentrations measured in three sewersheds corresponded to the relative prevalence of COVID-19 infection determined via clinical testing. Lastly, controlled experiments indicate that the 4S method prevented RNA degradation during storage of wastewater samples, was compatible with heat pasteurization, and could be performed in approximately 3 hours. Overall, the 4S method is promising for effective, economical, and accessible wastewater-based epidemiology for SARS-CoV-2, providing another tool to fight the global pandemic., ART

Objectives Determine whether the Heart Rate Variability Dysfunction score, a novel age-normalized measure of autonomic nervous system dysregulation, is associated with the development of new or progressive multiple organ dysfunction syndrome or death in critically ill children. Design, setting, and patients This was a retrospective, observational cohort study from 2012 to 2018. Patients admitted to the PICU with at least 12 hours of continuous heart rate data available from bedside monitors during the first 24 hours of admission were included in the analysis. Interventions None. Measurements and main results Heart rate variability was measured using the integer heart rate variability, which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The Heart Rate Variability Dysfunction score was derived from age-normalized values of integer heart rate variability and transformed, so that higher scores were indicative of lower integer heart rate variability and a proxy for worsening autonomic nervous system dysregulation. Heart Rate Variability Dysfunction score performance as a predictor of new or progressive multiple organ dysfunction syndrome and 28-day mortality were determined using the area under the receiver operating characteristic curve. Of the 7,223 patients who met inclusion criteria, 346 patients (4.8%) developed new or progressive multiple organ dysfunction syndrome, and 103 (1.4%) died by day 28. For every one-point increase in the median Heart Rate Variability Dysfunction score in the first 24 hours of admission, there was a 25% increase in the odds of new or progressive multiple organ dysfunction syndrome and a 51% increase in the odds of mortality. The median Heart Rate Variability Dysfunction score in the first 24 hours had an area under the receiver operating characteristic curve to discriminate new or progressive multiple organ dysfunction syndrome of 0.67 and to discriminate mortality of 0.80. These results were reproducible in a temporal validation cohort. Conclusions The Heart Rate Variability Dysfunction score, an age-adjusted proxy for autonomic nervous system dysregulation derived from bedside monitor data is independently associated with new or progressive multiple organ dysfunction syndrome and mortality in PICU patients. The Heart Rate Variability Dysfunction score could potentially be used as a single continuous physiologic biomarker or as part of a multivariable prediction model to increase awareness of at-risk patients and augment clinical decision-making.

Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality.Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes.The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components.In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227).Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

Objective To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLAⓇ) containing levonorgestrel (LNG) and ethinyl estradiol (EE). Study design This single-arm, open-label, multicenter, 1-year (13 cycle), phase 3 study enrolled sexually active women ≥18 years old at risk for pregnancy irrespective of body mass index (BMI). Women used patches in 28-day cycles (3 consecutive administrations of 7-day patches followed by 7 days off-treatment/patch-free week). We assessed contraceptive efficacy by the Pearl Index (PI) in women 18 to 35 years, excluding cycles without intercourse or when other contraceptive methods were used. Results The study enrolled 2032 demographically diverse women in the US, of which 35.3% had a BMI ≥30 kg/m2. In the primary efficacy analysis, the PI (95% confidence interval) was 5.8 (4.5–7.2) pregnancies per 100 woman-years. PIs trended higher as BMI increased; the PI was 4.3 (2.9–5.8) in women with BMI Conclusions The low-dose LNG/EE TDS was effective in preventing pregnancy in a population of women representative of US demographics. Efficacy was reduced in women with BMI ≥30 kg/m2. The TDS safety and tolerability profile was consistent with other similar dose combined hormonal contraceptives. Results of this phase 3 study supported the US Food and Drug Administration approval of TWIRLAⓇ for prevention of pregnancy in women with BMI Implications TDS (120 µg/day levonorgestrel and 30 µg/day ethinyl estradiol) is an effective, low-dose transdermal contraceptive patch with favorable tolerability profile approved for prevention of pregnancy in women with BMI

Background Large volumes of non-resuscitation fluids are often administered to critically ill children. We hypothesize that excess maintenance fluid is a significant contributor to non-resuscitation fluid and that non-resuscitation fluid administered beyond hydration requirements is associated with worse clinical outcomes in critically ill children. Methods We evaluated all patients admitted to two large urban pediatric intensive care units (PICU) between January 2010-August 2016 and January 2010-August 2018, respectively, who survived and remained in the hospital for at least 3 days following PICU admission. The primary outcome was in-hospital mortality. Association of excess fluid with outcomes was adjusted for confounders (age, Pediatric Risk of Mortality III score, study site, day 3 acute kidney injury, PICU era, resuscitation volume, and volume output) using multivariable regression. Results We evaluated 14,483 patients; 52% received non-resuscitation fluid in excess of hydration requirements. Non-resuscitation fluid in excess of hydration requirements was associated with higher in-hospital mortality after adjustment for confounders (adjusted odds ratio 1.01 per 10 mL/kg in excess fluid, 95% confidence interval: 1.002-1.02). Conclusions Non-resuscitation fluid in excess of hydration requirements is associated with increased mortality in critically ill children. Excess maintenance fluid is a modifiable contributor to this fluid volume. Strategies to reduce excess maintenance fluids warrant further study. Impact Critically ill children frequently receive non-resuscitation fluid in excess of their estimated hydration requirements. Non-resuscitation fluid volume in excess of estimated hydration requirements is associated with higher morbidity and mortality in critically ill children. Critically ill children receive a large volume burden from maintenance fluid. Maintenance fluid represents a modifiable contributor of non-resuscitation fluid in excess of hydration requirements. Strategies focused on limitation of maintenance fluid warrant further study.

Background: The prevalence of diabetes mellitus (DM) continues to increase among patients undergoing total hip arthroplasty (THA). It is unclear how insulin use is correlated with risk for adverse outcomes. Methods: A cohort of 146,526 patients undergoing primary THA were identified in the 2005–2017 National Surgical Quality Improvement Program database. Patients were classified as insulin-dependent diabetic (IDDM), non-insulin-dependent diabetic (NIDDM), or not diabetic. Multivariate analyses were used. Results: Compared to patients without diabetes, patients with NIDDM were at increased risk for 4 of 17 perioperative adverse outcomes studied. Patients with IDDM were at increased risk for those 4 and 8 additional adverse outcomes (12 of the 17 studied). Conclusion: These findings have important implications for preoperative risk stratification and quality improvement initiatives.

Inverted papilloma (IP) is a common proliferation of squamous epithelial cells of the sinonasal tract. Although considered benign, IP is known to cause local destruction, has a high rate of recurrence, and a low, but significant rate of malignant transformation. Differentiating an IP from its histologic mimickers is essential for appropriate risk stratification and long-term surveillance. A classic case of sinonasal inverted papilloma is discussed.

The results of a comparison on active power meter calibrations at the National Institute of Standards and Technology (NIST) using a source of ac power referenced to either a programmable Josephson voltage standard (PJVS) or a Josephson arbitrary waveform synthesizer (JAWS) is presented. The measurements were made at 60 V rms, 5 A rms, and 50 Hz at a power factor of 1.0. The estimated uncertainty of the active power applied to a meter under test (MUT) of the two system configurations is within $2~\mu \text{W}$ /VA ( $k = 1$ ), and the comparison results demonstrate that the two system configurations agree to within 1 part in $10^{6}$ for applied voltage, current, and phase. A discussion of the measurement techniques and major sources of error is given for applied power signals over the 50-Hz–6-kHz frequency range.

With the increasing popularity of alternative payment models, minorities who use more postacute care resources may face difficulties with access to quality total hip arthroplasty (THA) and total knee arthroplasty (TKA) care. The purpose of this study is to compare differences in perioperative complications and functional outcomes between African American and Caucasian patients undergoing THA and TKA.We reviewed a consecutive series of all primary THA and TKA patients at our institution from 2015 to 2018. Demographics, comorbidities, 90-day complications, readmissions, Veterans Rand 12-Item Health Survey (VR-12), Hip disability Osteoarthritis Outcome Score (HOOS), and Knee injury and Osteoarthritis Outcome Scores (KOOS) were compared between African American and Caucasian patients. A multivariate analysis was performed to control for confounding variables.Of the 5284 patients included in the study, 1041 were African American (24.5%). Although African American patients had lower preoperative HOOS/KOOS (33.5 vs 45.1, P.001) and mental VR-12 scores (37.8 vs 51.5, P.001) compared with Caucasian patients, there was no clinical difference at 1 year in HOOS/KOOS (50.2 vs 50.4), mental VR-12 (55.0 vs 52.6), or physical VR-12 scores (39.5 vs 39.8). When controlling for demographics and medical comorbidities, African American race was associated with increased rehabilitation facility discharge (odds ratio, 1.69; P.001) but no difference in readmissions or complications.Although African American patients had lower preoperative functional scores, they made improved postoperative gains when compared with Caucasian patients. Although there was no difference in postoperative complications, further studies should assess social causes for the increase in rehabilitation utilization rates in minority patients.

Introduction In global health engagement settings, performance of oncologic surgery is evaluated by understanding the host nation healthcare capacity to include inpatient care support and the available postoperative adjunctive therapy to include chemotherapy and radiation therapy. Materials and Methods We present a case during Pacific Partnership 2018 of a patientwith a malignant facial mass diagnosed postoperatively. A literature review was conducted, searching specifically for cases related to pleomorphic adenoma (PA), carcinoma ex-PA, cases of misdiagnosis, and global health engagement operations. Results The patient presented without constitutional symptoms, clinical lymphadenopathy, or cranial nerve VII weakness with a preoperative host nation diagnosis of a benign salivary neoplasm (PA). Postoperatively, a gross total resection of the mass was diagnosed as high-grade adenocarcinoma—a carcinoma ex-PA of the parotid gland. Oncologic staging was noted to be advanced at T3N0, and the patient was referred back to the host nation surgeons for radiation oncology consultation and clinical surveillance to follow. Discussion Diagnosis of carcinoma ex-PA—a rare form of salivary gland malignancy—is not always straightforward because of its high degree of cellular heterogeneity, leading to inconsistencies in preoperative sampling results. This case addresses the preoperative diagnostic challenges associated with this type of malignancy, different types of possible treatment modalities aimed at reducing postoperative morbidity, and the preoperative and postoperative challenges that are critical to address during health engagement operations.

Background Regular physical activity (PA) promotes health and can prevent and treat diseases among both humans and dogs. Unfortunately, most U.S. adults do not meet PA recommendations, and many dogs are also insufficiently active. Veterinary-prescribed PA programs have shown some success in increasing activity among overweight dogs, but the impacts of such programs have not yet been tested for efficacy among otherwise-healthy dogs and owners. In addition, although wearable devices that monitor PA and provide individuals with feedback (e.g., progress toward a daily step goal) can effectively increase human PA, it is unclear what impact similar wearable devices have on human and dog PA when the PA-monitoring devices are worn by dogs. The present study assessed the impact of an 8-week veterinary-prescribed PA program on activity and health among dogs and their owners, and randomized participants (n = 59) to two groups: one in which PA was measured but not visible to participants (n = 30), and one in which PA was measured and real time feedback was visible through a wearable device (n = 29). Results Participants in both groups showed significant PA increases over the course of the 8-week program. Biomedical testing performed at the veterinary clinic facilitated early diagnosis of systemic illness in one human participant. The frequency of hypertension in human participants decreased significantly from baseline to the end of the program (week 8). Other health indices (e.g., BMI in humans, body weight and BCS in dogs) improved, albeit not to a statistically significant extent, over the course of the program. There were no significant differences on the outcomes of interest between the two experimental conditions. Conclusions Veterinary-prescribed PA programs appear promising for increasing PA among insufficiently active but otherwise healthy dogs as well as their owners. Additional testing of veterinary-prescribed PA is warranted, particularly at other types of veterinary clinics (e.g., private practices). Incorporating wearable devices permitting owners to track canine PA did not appear necessary for obtaining these benefits; however, additional studies investigating alternative devices or different time periods may be warranted.

BackgroundIncreased chloride in the context of intravenous fluid chloride load and serum chloride levels (hyperchloremia) have previously been associated with increased morbidity and mortality in select subpopulations of intensive care unit (ICU) patients (e.g patients with sepsis). Here, we study the general ICU population of the Medical Information Mart for Intensive Care III (MIMIC-III) database to corroborate these associations, and propose a supervised learning model for the prediction of hyperchloremia in ICU patients.MethodsWe assessed hyperchloremia and chloride load and their associations with several outcomes (ICU mortality, new acute kidney injury [AKI] by day 7, and multiple organ dysfunction syndrome [MODS] on day 7) using regression analysis. Four predictive supervised learning classifiers were trained to predict hyperchloremia using features representative of clinical records from the first 24h of adult ICU stays.ResultsHyperchloremia was shown to have an independent association with increased odds of ICU mortality, new AKI by day 7, and MODS on day 7. High chloride load was also associated with increased odds of ICU mortality. Our best performing supervised learning model predicted second-day hyperchloremia with an AUC of 0.76 and a number needed to alert (NNA) of 7—a clinically-actionable rate.ConclusionsOur results support the use of predictive models to aid clinicians in monitoring for and preventing hyperchloremia in high-risk patients and offers an opportunity to improve patient outcomes.

PURPOSE: Determine baseline clinical skills of medical students entering the Obstetrics and Gynecology (OB/GYN) clerkship with prior clinical curricular exposure. BACKGROUND: Students are introduced to clinical correlates sooner in the preclinical curriculum to facilitate adult learning. There are few studies determining clerkship-specific clinical skills readiness in OB/GYN, a specialty with historically limited previous exposure. METHODS: An anonymous 15-question clinical readiness survey (1–5 Likert scale) was administered to medical students during their OB/GYN Orientation at the University of Texas Health Science Center San Antonio over four academic years, 2014–2018, to determine baseline OB/GYN clinical skill knowledge and confidence. Statistical analysis included Spearman rank correlation and Kruskal-Wallis tests, with significance defined as p < 0.05. RESULTS: The survey was completed by 346 students (77% participation). Overall, students felt most confident in knot tying skills (17%) and closed gloving technique (7%) and least confident in knowledge of labor curve (86%), Leopold’s maneuvers (88%), and Montevideo units (MVU) (90%). Confidence in performing closed gloving (4% vs. 11%, p < 0.01) and tying knots (8% vs. 27%, p < 0.01) was significantly higher during rotations later in the academic year. Students who expressed a higher level of interest felt more prepared for the clerkship (rs = 0.21, p < 0.01). DISCUSSION: Results indicate that confidence in obstetric-specific clinical skills is relatively low throughout the academic year; however, baseline surgical skills show improvement. It is important for teaching faculty to know baseline clinical skills of the medical student with earlier clinical exposure to enhance adult learning and optimize clinical competency. In medical students receiving earlier clinical exposure, confidence in baseline obstetric-specific clinical skill is relatively low throughout the academic year. Confidence in general surgical skills demonstrates improvement over the academic year.

Objectives Individuals with type 2 diabetes are at risk for deficits in instrumental activities of daily living (IADL: e.g., managing medication, preparing healthy meals). Understanding which demographic and health factors contribute to decreased frequency of IADL performance is especially important to prevent age-related functional decline in type 2 diabetes. This study examined the relationships among demographic and health variables and frequency of IADL performance in adults with type 2 diabetes. Methods For this cross-sectional study, we collected health, demographic, and activity information via self-report and electronic health record review from safety-net primary care patients with type 2 diabetes (n = 93). We used regression models to determine which factors were associated with IADL performance in three subscales (domestic, leisure/work, outdoor) and the overall score. Results Depression was associated with decreased frequency of IADL performance for domestic, leisure/work, and outdoor activities. Each additional daily medication was associated with decreased frequency of domestic and outdoor IADL performance. Discussion Depression and taking more daily medication were predictors of decreased IADL performance for adults with type 2 diabetes. Our findings suggest regular screening for depression and polypharmacy is important in the primary care of diabetes; especially as these are potentially modifiable risk factors.

Purpose As health systems continue to expand pharmacy and clinical services, the ability to evaluate potential medication safety risks and mitigate errors remains a high priority. Workload and productivity monitoring tools for the assessment of operational and clinical pharmacy services exist. However, such tools are not currently available to justify medication safety pharmacy services. The purpose of this study is to determine methods used to assess, allocate, and justify medication safety resources in pediatric hospitals. Methods A 32-question survey was designed and distributed utilizing the Research Electronic Data Capture (REDCap) tool. The survey was disseminated to 46 pediatric hospitals affiliated with the Children’s Hospital Association (CHA). The survey was distributed in October 2018, and the respondents were given 3 weeks to submit responses. Data analysis includes the use of descriptive statistics. Categorical variables were summarized by frequencies and percentages to distinguish the differences between pediatric health systems. Results Of 26 respondents, 15.4% utilized metrics to justify medication safety resources. Metrics utilized were based on medication dispenses, projects, and error coding. Twenty-three percent of respondents were dissatisfied with current pharmacy-based medication safety resources within the organization. There was variability of medication safety resources within pediatric hospitals, including the number of dedicated full-time equivalents, time spent on tasks, and task prioritization. Conclusion Assessing medication safety resources at various pediatric hospitals highlights several potential barriers and opportunities. This information will serve as the foundation for the creation of a standardized workload assessment tool to assist pharmacy leaders with additional resource justification.

Anal fissure has a very large number of treatment options. The choice is difficult. To assist in this choice, presented herein is a summary of a systematic review and meta-analysis of all published treatments for anal fissure that have been studied in randomized controlled trials up through 2016. The review is divided into those studies that compared two or more surgical procedures and those that had at least one arm that was nonsurgical. Studies were further categorized by the specific interventions and comparisons. The outcome assessed was the inverse of sustained cure of the fissure, i.e., treatment failure. In addition, the harms of treatment assessed were headache and anal incontinence. Risk of bias was assessed for each study and the strength of the evidence of each comparison was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A total of 148 eligible trials were found and assessed, 31 in the surgical group (2606 patients) and 117 in the nonsurgical group (9456 patients). There were 14 different operations described in the surgical group and 29 different nonsurgical treatments in the nonsurgical group along with partial lateral internal sphincterotomy (LIS). There were 61 different comparisons. Of these, 47 were reported in two or fewer studies, usually with quite small populations. The largest single comparison was glyceryl trinitrate (GTN) versus control with 19 studies. GTN was more effective than control in terms of sustained cure (odds ratio = 0.68; 95% confidence interval = 0.63–0.77) but the quality of evidence was very poor due to severe heterogeneity and risk of bias due to inadequate clinical follow-up. The only comparison to have a high GRADE quality of evidence was a subgroup analysis of LIS versus any medical therapy, with outcome of treatment failure (0.12; 0.07–0.21) and mild incontinence (4.41; 1.97–9.87) assessed after at least 6 months from surgery. There were 12 studies in this analysis, the medical therapy being GTN in 6, Botox in 5, and calcium channel blocker (CCB) in 1. Most of the other analyses were downgraded in GRADE due to imprecision, i.e., too few or too small studies, and significant heterogeneity in almost all other comparisons with more than six studies. LIS is superior to nonsurgical therapies in achieving sustained cure of fissure with an increased risk of mild incontinence, usually meaning flatus. CCBs were more effective than GTN and had less risk of headache, but with only a low quality of evidence. Anal incontinence, once thought to be a frequent risk with LIS, was found in various subgroups in this review to have a risk between 3.4 and 4.4%. Among the surgical studies, manual anal stretch (Lord procedure) performed worse than LIS in the treatment of chronic anal fissure in adults. For those patients requiring surgery for anal fissure, open LIS and closed LIS appear to be equally efficacious, with a moderate GRADE quality of evidence. Most other GRADE evaluations of procedures were low to very low, due mostly to imprecision.

Objectives Methamphetamine (MA) is a widely used illicit drug and a nationwide public health concern. Although dental complications are consistently reported among MA users, yet limited nationally representative studies on the associations between MA use and oral health currently exist. Methods Using the National Health and Nutrition Examination Survey 2009-2014, we analyzed 8,762 respondents aged 30-64 years who had completed a periodontal examination. MA use was self-reported; periodontitis, untreated caries, and missing teeth were assessed by calibrated dentists. Descriptive statistics as well as multivariable regression analyses were performed. Data were weighted to yield representative estimates of the US adult population. Results Overall 7.8 percent of US adults aged ≥30 years had ever used MA. Ever-use prevalence was higher among males, whites, and individuals below the federal poverty level. Established MA users had a higher prevalence of untreated dental caries (36.6 percent), any periodontitis (54.8 percent), and severe periodontitis (12.2 percent) than those who had never used MA. The prevalence of any periodontitis was higher among current MA users (PR: 1.31; 95% CI: 1.05-1.62) than those who never used MA. Prevalence of untreated dental caries was higher among current MA users (PR: 1.53; 95% CI: 1.10-2.13) and established users (PR: 1.21; 95% CI: 1.02-1.48) than never users. Taking MA orally and/or through injection was associated with higher odds of severe periodontitis than orally only (AOR: 3.72; CI: 1.79-7.75). Conclusions MA users had a higher prevalence of periodontitis and dental caries. Continued research assessing the relationship between MA use and oral health can inform clinical interventions and management of dental diseases in MA users.

Objective Characterize firefighters' acute stress and tiredness by duty status (ie, "off night/day," "on night/day"). Methods Thirty nine career firefighters completed three, eight-day smartphone-based ecological momentary assessment periods with seven surveys per day assessing stress and tiredness. Mixed-effects location scale models examined duty status effects on stress and tiredness. Results Firefighters' lowest stress and tiredness levels were when off-duty (β = 16.27 and β = 24.71, respectively) and their highest levels were when on-duty (β = 24.47 and β = 32.18, respectively). Within-subject effects of duty status accounted for a larger proportion of variability in stress and tiredness for all duty types, except for stress when "on-duty night/off-duty day." Conclusions Firefighters had more similar stress and tiredness outcomes when they were on-duty and less similar outcomes when off-duty. This could be due to firefighters having more similar experiences when they are on- versus off-duty.

The benefit of adding oral antibiotic prophylaxis (OA) to intravenous prophylaxis (IV) in elective colorectal surgery to prevent surgical site infection (SSI) and whether the benefit of OA requires a mechanical bowel cleansing (MBP) are assessed in a systematic review. Meta-analyses compare randomized trials of IV versus IV plus OA, both with MBP; OA versus IV plus OA, both again with MBP; OA plus IV in studies randomizing patients to MBP or no MBP; and IV versus IV plus OA in patients with no MBP. MEDLINE, EMBASE, and the Cochrane Library were searched for eligible studies from 1965 to April 1, 2020. The outcome assessed was SSI, superficial and deep, but not organ space. For each included study, risk of bias was assessed using the Cochrane Risk of Bias tool version 1. For each comparison, meta-analysis was performed from data from eligible studies to obtain a summary effect and heterogeneity using RevMan. Sensitivity analyses were performed excluding studies of poor quality. Certainty of evidence was assessed using GRADE for each comparison. Sixty-one studies published in 1971–2020 from 55 publications reporting 12,297 patients were eligible for inclusion. A total of 36 studies compared IV to OA plus IV with MBP. The risk ratio (RR) and 95% confidence interval (CI) for SSI with oral and IV vs. IV alone are 0.47, 0.40–0.56. The RR in 19 studies for IV plus OA versus OA alone is 0.48, 0.38–0.62. The RR for OA plus IV with MBP versus without MBP in 5 studies is 1.17, 0.84–1.64. The RR for OA plus IV versus IV alone when no bowel prep was used in two studies is 0.36, 0.18–0.72. RRs were similar in sensitivity analyses. The GRADE is high for the first two comparisons, moderate for the 3rd, and low for the 4th due to imprecision and heterogeneity. Combined OA and IV is superior to either alone in preventing SSI. The certainty of evidence is such that further research is unlikely to alter this relationship when MBP is used. In randomized trials of MBP, OA plus IV shows no benefit from MBP versus no MBP. The last comparison shows in just two studies that as in the first meta-analysis, but in the absence of MBP, combined OA plus IV is also superior to IV alone.

The COVID-19 pandemic has disrupted every aspect of society in a way never previously experienced by our nation's orthopaedic surgeons. In response to the challenges the American Board of Orthopaedic Surgery has taken steps to adapt our Board Certification and Continuous Certification processes. These changes were made to provide flexibility for as many Candidates and Diplomates as possible to participate while maintaining our high standards. The American Board of Orthopaedic Surgery is first and foremost committed to the safety and well-being of our patients, physicians, and families while striving to remain responsive to the changing circumstances affecting our Candidates and Diplomates.

BACKGROUND: Total joint arthroplasty is one of the most common surgeries performed in the United States with total knee arthroplasty (TKA) being one of the most successful surgeries for restoring function and diminishing pain. Even with the demonstrated success of TKA and a higher prevalence of arthritis and arthritis related disability among minorities, racial and gender disparity remains a constant issue in providing care for the adult reconstruction patient. AIM: To assess the role of demographics and expectations on differences in perioperative patient reported outcomes (PRO) following TKA. METHODS: One hundred and thirty-three patients scheduled for primary unilateral TKA secondary to moderate to severe osteoarthritis were enrolled in this two-institution prospective study. Validated PRO questionnaires were collected at four time points. Statistical analysis was conducted to determine the impact of gender, ethnic background and expectation surveys responses to assess PRO at these time points. RESULTS: Females were associated with worse preoperative Knee Injury and Osteoarthritis Outcome Scores (KOOS) for symptoms, pain, and activities of daily living. African Americans were associated with worse KOOS for pain, activities of daily living, and quality of life. Despite worse preoperative scores, no difference was noted in these categories between the groups postoperatively. Additionally, all pre-operative psychometric scales were equivalent across groups except Geriatric Depression scale, which was significantly different between groups within the Race and Age Group (P < 0.05). Conversely, Pain Catastrophizing Scale, was significantly different for all subscales and total score within Age Group (P < 0.05), and the Magnification, Helplessness subscales as well as the Total score were significantly different between groups for Race and Relationship Status (P < 0.01). CONCLUSION: We conclude that female and African American patients have lower preoperative KOOS scores compared to white male patients. No postoperative differences in outcomes between these groups.

Objective The Accreditation Council for Graduate Medical Education and the Council on Resident Education in Obstetrics and Gynecology have milestones and/or competencies relating to colposcopy; however, the optimal way to reach these objectives is not proscribed and left to individual programs. Here, we aim to assess resident skill, confidence levels, perceived level of knowledge, and satisfaction with colposcopic training before and after implementation of a new interactive learning module with visual feedback. Materials and methods A new online educational intervention was developed by the author (E.L.N.) based on adult learning theory and introduced into our obstetrics and gynecology resident colposcopy curriculum in July 2014. We assessed performance on an objective competency examination administered at baseline and repeated after 6 months of our 24 residents.In addition, we assessed resident confidence levels, perceived level of knowledge, and satisfaction with training before and 6 months after intervention. Results Scores on a national online examination improved after the intervention (p = .014). Significant improvements on the examination were seen in the sections of medical knowledge (p = .031) and management (p = .011). Residents' perceived knowledge increased significantly after the intervention (p = .030). Conclusions Learning outcomes improved after introduction of a novel teaching intervention.

Continuing to 36 months, the phase 2 study of a low-dose copper intrauterine device with a nitinol frame showed high efficacy and safety., OBJECTIVE: To assess in parous and nulliparous women, the efficacy, safety, and tolerability of a new, low-dose copper (175 mm2) intrauterine contraceptive with a flexible nitinol frame provided in a preloaded applicator. METHODS: Institutional review boards at 12 U.S. sites approved this commercially funded project. Patients met standard inclusion and exclusion criteria for a copper-based intrauterine device (IUD), generally consistent with the Centers for Disease Control and Prevention's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. Intrauterine device placement occurred at any day in the eligible patient's menstrual cycle after assuring she was not pregnant. The primary outcome measure assessed efficacy (measured by the Pearl Index) in this 1-year study with a 2-year extension. Secondary outcomes included placement success, ease of placement, safety as measured by adverse events, and tolerability assessed by discontinuation rate and bleeding and spotting patterns. RESULTS: A total of 286 women provided 5,640 cycles evaluable for pregnancy. Patients averaged 27.1 years of age. Nulliparous women represented 60.8% of the patients. Over 36 months of observation, we identified two pregnancies (Pearl Index 0.46 [95% CI 0.06–1.67]) and 10 serious adverse events; none were study-related. Successful placement occurred in 283 participants (99.0%). Median (range) continuation times were 2.7 years (0–3.4). We identified five expulsions (1.8%), zero uterine perforations, and one report of pelvic inflammatory disease. Adverse events prompted 30 women (10.6%) to discontinue early in the first year of use with 23 (8.1%) discontinuing for issues of bleeding, pain, or both. Altogether, 107 (37.8%) completed 36 months of device use. Mean bleeding days per cycle decreased from 7.6 in cycle 1 to 5.2 in cycle 13. CONCLUSION: The novel, low-dose copper and nitinol IUD demonstrated high efficacy and safety in this phase 2 U.S. Food and Drug Administration trial and warrants further expanded study in a phase 3 clinical trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02446821. FUNDING SOURCE: Sebela Pharmaceuticals, Inc.

As news publishers continue to lose subscribers and advertising revenue, journalism practitioners and researchers have looked to newcomers to the field for ideas of how to adapt and succeed in a much more saturated and unstable media environment. Many have specifically looked to digital native news organizations to understand the ways that journalism is attempting to reinvent itself for a media landscape that is very different from the previous one. Yet what often gets lost in this focus on the newest news organizations is the resilience of many of journalism’s older ones. In this study, I analyze a year’s worth of U.S.-based online news consumption data to show that, even in a media environment increasingly saturated with digital native news outlets, legacy news brands continue to comprise a majority of the most popular news sites. Drawing on audience studies literature, I argue that these findings likely reflect audience preferences for familiar, established brands, as well as structural advantages these brands maintain due to their size and capital. I conclude that the fate of digital news organizations is not just a question of their innovativeness or nimbleness. It is also a question of their ability to combat a combination of powerful, stubborn forces: the habits of the people they hope to reach, and the deep pockets of their competitors.

Objectives The primary objective of the current study is to describe the prevalence and profile of cognitive domains affected in older adults with hematological malignancies evaluated for hematopoietic cell transplantation (HCT) using the Montreal Cognitive Assessment (MoCA) and neuropsychological tests. The secondary objective is to determine if a specific MoCA cut-off score would correlate with the identification of cognitive impairment detected by neuropsychological tests. This would facilitate interpretation of cognitive screening and referral of patients who would likely need further neuropsychological testing. Materials and Methods Fifty-one patients 60 years and older who were evaluated for HCT were assessed using a battery of standardized neuropsychological tests and MoCA. We analyzed Receiver Operating Characteristics (ROC) comparing MoCA scores and four different neuropsychological test criteria for cognitive impairment. Results The prevalence of cognitive impairment detected by neuropsychological tests was 53 to 70.6% using the criteria for patients with cancer by the International Cancer Cognition Task Force (ICCTF). The following cognitive domains were most affected: language, learning and memory, visuospatial skills, and executive function. MoCA is an appropriate screening test for cognitive impairment. Using the ICCTF criteria, 86 to 100% of patients are correctly classified as having significant cognitive impairment on neuropsychological tests using a cut-off score of 20 or less. Conclusion There is a high prevalence of cognitive impairment identified by neuropsychological tests in older patients with hematological malignancies evaluated for HCT. Identification of an appropriate MoCA cut-off score in this population is important to identify patients who would benefit from further assessment.

BACKGROUND: It is well known that medication accessibility reduces morbidity and mortality and increases health-related quality of life; however, despite efforts to improve health care access, many...

This protocol for a Cochrane Review is out of date. The authors have abandoned it.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the global pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it to the host response to respiratory syncytial virus (RSV) and influenza virus (IV). We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with IV, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an interferon response in the nasal mucosa. The magnitude of the interferon response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2-infected adults had increased expression of genes involved in neutrophil activation and T cell receptor signaling pathways compared to SARS-CoV-2-infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Inflammatory biomarker C-reactive protein (CRP) is associated with breast cancer risk and survival. We examined whether CRP levels before radiotherapy (pre-RT), after RT (post-RT), and RT-induced change impact breast cancer progression-free survival (PFS). Methods Plasma high-sensitivity CRP was measured, and patients were followed for up to 13 years after RT. PFS was calculated from the date of diagnosis to the date of disease progression or the last date of follow-up. Univariable and multivariable Cox proportional hazards regression models were used to evaluate the associations between CRP and PFS adjusted for other patient/clinical variables. Results In 469 patients (64 non-Hispanic Whites, 303 Hispanic Whites, and 102 African Americans), post-RT CRP levels were significantly higher in patients with progression compared to progression-free patients (mean±SD: 12.2±15.4 mg/L vs. 7.3±11.5, p=0.011). In univariable analyses, worse PFS was significantly associated with post-RT CRP ≥5.1 mg/L (hazard ratio [HR]: 2.67; 95% confidence interval [95% CI]: 1.65-4.30) and CRP change ≥2.3 mg/L (HR: 3.55; 95% CI: 2.25-5.64). In multivariable models, post-RT CRP ≥5.1 mg/L was associated with worse PFS in all (HR: 2.10; 95% CI: 1.29-3.42) or patients with tumor stage III (HR: 2.93, 95% CI: 1.20-7.18). CRP change ≥2.3 mg/L was associated with worse PFS in all (HR: 2.38; 95% CI: 1.45-3.92) or patients with tumor stage III (HR: 2.41, 95% CI: 1.09-5.33). Conclusions Our data suggest that an RT-induced hyper-inflammatory response may contribute to worse breast cancer PFS. Future larger studies are warranted to validate our findings and guide follow-up surveillance and targeted interventions.

A high-risk left-sided posterolateral manifest accessory pathway (AP) was identified in a 49-year-old man. Two prior ablations had failed. A repeat procedure using 3D electroanatomic mapping demonstrated an extremely oblique AP. The earliest atrial activation site was not amenable to endocardial ablation. The earliest ventricular activation site was identified, demonstrating an AP with an extremely slanted course. Radiofrequency ablation here resulted in sustained bidirectional AP block. In challenging AP ablation cases, recognition of the potential for an oblique AP and the use of electroanatomic mapping may be beneficial.

Background Prescription opioids play a large role in the opioid epidemic. Even short-term prescriptions provided postoperatively can lead to dependence. Objective To provide opioid prescription recommendations after Mohs micrographic surgery (MMS) and reconstruction. Methods This was a multi-institutional Delphi consensus study consisting of a panel of members of the American College of Mohs Surgery from various practice settings. Participants were first asked to describe scenarios in which they prescribe opioids at various frequencies. These scenarios then underwent 2 Delphi ratings rounds that aimed to identify situations in which opioid prescriptions should, or should not, be routinely prescribed. Consensus was set at ≥80% agreement. Prescription recommendations were then distributed to the panelists for feedback and approval. Results Twenty-three Mohs surgeons participated in the study. There was no scenario in which consensus was met to routinely provide an opioid prescription. However, there were several scenarios in which consensus were met to not routinely prescribe an opioid. Conclusion Opioids should not be routinely prescribed to every patient undergoing MMS. Prescription recommendations for opioids after MMS and reconstruction may decrease the exposure to these drugs and help combat the opioid epidemic.

Brian Pecson and Daniel Gerrity present an Editorial Perspective which focuses on the impact of SARS-CoV-2 on the water industry.