Adverse mental and emotional health outcomes are increasingly recognized as a public health challenge associated with the COVID-19 pandemic.The goal of this study was to examine the association of COVID-19 risk misperceptions with self-reported household isolation, a potential risk factor for social isolation and loneliness.We analyzed data from the Franklin Templeton-Gallup Economics of Recovery Study (July to December 2020) of 24,649 US adults. We also analyzed data from the Gallup Panel (March 2020 to February 2021), which included 123,516 observations about loneliness. The primary outcome was self-reported household isolation, which we defined as a respondent having no contact or very little contact with people outside their household, analogous to quarantining.P<.001 at each time point). Characteristics associated with self-reported household isolation from the July and August 2020 surveys and persisting in the December 2020 survey included younger age (18 to 39 years), having a serious medical condition, having a household member with a serious medical condition, and identifying as a Democrat. In the Gallup Panel, self-reported household isolation was associated with a higher prevalence of loneliness.From July to December 2020, 53% to 57% of respondents reported living in household isolation. Most participants reported beliefs about COVID-19 health risks that were inaccurate, and overestimation of health risk was most common. For example, while deaths in persons younger than 55 years old accounted for 7% of total US deaths, respondents estimated that this population represented 43% of deaths. Overestimating COVID-19 health risks was associated with increased self-reported household isolation, with percentage differences ranging from 5.6 to 11.8 (Pandemic-related harms to emotional and mental well-being may be attenuated by reducing risk overestimation and household isolation preferences that exceed public health guidelines. Adverse mental and emotional health outcomes are increasingly recognized as a public health challenge associated with the COVID-19 pandemic. As early as March 2020, a national survey reported that 36% of US adults felt the pandemic would have a serious impact on their mental health .These health sequalae of the COVID-19 pandemic are multifactorial, and social isolation is likely an important contributor ,6. BecauThe US Centers for Disease Control and Prevention (CDC) recently recommended that researchers examine drivers of adverse mental health during the COVID-19 pandemic . One driWe used data from the Franklin Templeton-Gallup Economics of Recovery Study, a self-administered web survey from an opt-in sample provided by Dynata of 24,649 US adults, aged 18 years and older, of whom 10,419 participated during more than one survey time point. The survey was conducted during the following time points: July 2 to 14, August 3 to 11, September 4 to 13, October 1 to 9, November 2 to 6, and December 1 to 7, 2020. Gallup weighted the obtained sample to correct for nonresponse and construct a nationally representative population. Nonresponse adjustments were made by adjusting the sample to match the national demographics of gender, age, race and ethnicity, region, educational level, marital status, and employment status. Demographic weighting targets were based on the Census Bureau’s 2018 data release of the American Community Survey and the Current Population Survey (February 2020).We also supplemented this survey with data from the Gallup Panel, a research panel that is representative of the US adult population and includes approximately 100,000 members. Gallup fielded the COVID-19 tracking survey on March 13, 2020, and collected approximately 1000 responses daily until April 26, 2020, when the sample declined to approximately 500 responses daily. The Gallup Panel’s COVID-19 Tracking Survey includes information about self-reported household isolation and loneliness, with 123,516 observations from March 24, 2020, to February 21, 2021. This study was exempt from institutional review board review according to policies of the UCLA  Office of the Human Research Protection Program.completely isolated (no contact) or mostly isolated (very little contact) from people outside their household. We assessed loneliness in the Gallup Panel survey by asking participants, “Did you experience the following feelings during a lot of the day yesterday?” Loneliness and other emotional experiences were included as response options. The specific questions and respondent options are provided in We assessed self-reported household isolation by asking participants about the degree of in-person contact outside their household that they had over the past 24 hours. We considered a participant to be isolated if they reported being We evaluated perceptions of COVID-19 health risks using multiple questions. In July and August, respondents were asked about the percentage of all US COVID-19 deaths that fell into the following age strata: age 24 years and below, age 25 to 34 years, age 35 to 44 years, age 45 to 54 years, age 55 to 64 years, and age 65 years and older. We assessed misperceptions using the reported proportion of deaths attributable to persons under the age of 55 years because most deaths from COVID-19 have occurred in persons older than 55 years. Perceptions about age-related COVID-19 health risks were assessed in September and October 2020 with an analogous question about the age distribution of COVID-19 hospitalizations.In the November 2020 survey, respondents were asked what percentage of patients hospitalized with COVID-19 died. In the December 2020 survey, respondents were asked what percentage of patients infected with COVID-19 required hospitalization.CDC data were used to estimate the proportion of deaths from COVID-19 by age. Data from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) was used to estimate hospitalizations by age . BecauseIn each wave, survey respondents were asked whether they or a household member had a comorbidity that increased the risk of severe COVID-19 illness. Respondents also reported sociodemographic characteristics, household income, and preferences for political parties. Per capita deaths from COVID-19 in each US county from March 1 until December 1 were assessed using CDC data .Descriptive analyses of respondents’ characteristics were performed using data from July, August, and December 2020. The July and August surveys were combined for analyses because questions about risk perception were identical between those two time points. The September and October surveys were similarly combined. We used multivariable logistic regression analyses to examine the relationship between misperceptions about COVID-19 health risks and social isolation. Results from these models were presented as predictive margins, in which the regression models were used to estimate the marginal effect of risk overestimation, expressed as a proportion, while holding the distribution of all other covariates constant . The adjPerceptions about risk were characterized as being overestimates, underestimates, or accurate estimates. To provide respondents with a reasonable degree of latitude and to account for any uncertainty in our reference estimates, we considered responses that were within 5 percentage points above or below the correct estimate as being accurate  . A rangeWe performed mean imputation from the overall sample for education (missing <1%), income (missing <1%), and whether the respondent or their family had a serious medical condition (missing <1%). We used this method instead of a more robust multiple imputation model because of the low rate of missingness. We did not report percentages as n/N values because all reported percentages were estimated using analytic weights. All analyses were performed using Stata 14 (StataCorp LP) and incorporated analytic weights to account for the effects of nonresponse.The data used in this study are available from the corresponding authors upon request and with the permission of Franklin Templeton and Gallup.We present descriptive characteristics of the respondents in Most participants held beliefs about COVID-19 health risks that were inaccurate . OverestThe proportion of respondents living in self-reported household isolation did not vary substantially over time, ranging from 53% to 57% . OverestCharacteristics associated with self-reported household isolation from the July and August 2020 surveys and persisting in the December 2020 survey included younger age (18 to 39 years), having a serious medical condition, having a household member with a serious medical condition, and identifying as a Democrat . Being BAdverse mental and emotional health effects of the COVID-19 pandemic are an increasingly recognized public health challenge. Risk misperceptions about COVID-19 may be exacerbating this challenge. Using Franklin Templeton-Gallup Economics of Recovery Study surveys from July to December 2020, we found that respondents consistently overestimated health risks associated with COVID-19, as measured by four different questions assessing COVID-19 morbidity and mortality. Overestimation of risk was consistently associated with greater self-reported household isolation, which may have adverse emotional and mental effects similar to quarantining ,7. TheseWhile social isolation and loneliness have often been considered health risks for older adults, prior research has shown that COVID-19–related emotional and mental health harms are disproportionately borne by younger adults ,17. A JuSuicidal ideation among young adults is a concern because it is associated with a markedly increased risk of suicide plan and attempt, particularly during the first year after onset of ideation . Among pRespondents who had a serious medical condition or lived with a household member with a serious medical condition were more likely to engage in self-reported household isolation. Based on public health messages about risk factors for an adverse COVID-19 outcome, this finding was anticipated. Our finding that political party was associated with differences in self-reported preventive health behavior for COVID-19 has been confirmed in other work, including a survey study of 3000 American adults performed in March 2020 . The parOur study has limitations. We asked respondents about household isolation over the previous 24 hours rather than over a longer period of time, which may have led to inaccuracies. However, the relatively stable distribution of self-reported household isolation from month to month suggests that a 24-hour recall period was informative. Although we measured self-reported household isolation, we could not quantify social isolation or loneliness for survey respondents in the Franklin Templeton-Gallup Economics of Recovery Study because we did not collect information about participation in group activities, social engagement with friends or relatives, or subjective experience of loneliness ,23. It iAnother limitation is that self-reporting bias may have affected the accuracy of our household isolation measure. However, the relatively stable distribution of self-reported household isolation across study periods suggests that this bias was minimal. In addition, the questions we used to assess risk perceptions changed over time, which precluded direct comparisons of risk perception between time periods. Another factor that further complicated measurement of COVID-19 health risks and the likelihood of reporting household isolation is that COVID-19 case levels varied during our study period. Our regression models adjusted for per capita COVID-19 cases at the county level, but there could be confounding effects from other pandemic factors that varied over time. Furthermore, despite differences in our survey questions related to COVID-19 risk perception, these questions consistently probed beliefs about hospitalization and mortality risk, and our finding of an association between risk overestimation and self-reported household isolation was consistent, despite the changing questions.In conclusion, survey respondents overestimated several health risks associated with COVID-19, and this overestimation was associated with a respondent’s decision to avoid contact with people outside the household. This relationship was consistent from July to December. Harms to emotional and mental well-being experienced by US adults during the COVID-19 pandemic may be mitigated by addressing risk misconceptions and attenuating household isolation preferences that exceed public health guidelines.


Entamoeba histolytica, the causal agent of amebiasis, is considered a worldwide emergent disease and still represents an important cause of death in Mexico. Here, we describe a clinical case, involving an inflammatory response to both Coronavirus Infectious Disease 2019 (COVID-19) and intestinal amebiasis 54-year-old, COVID-positive Mexican gentleman was admitted to surgery following 6 days of hematochezia. An exploratory laparotomy and colonoscopy revealed multiple fibrous and amebic ulcerations (5–10 cm in diameter), with necrotic tissue predominantly localized in the sigmoid, descending and ascending colon. We discuss the pathophysiological interplay of both COVID-19 and intestinal amebiasis with the aim of highlighting a potentially novel aggravating mechanism in surgical patients suffering from colonic perforation in the setting of abdominal sepsis.The parasite  Entamoeba histolytica, an anaerobic protozoan spread through fecal–oral transmission. Pathogenicity includes adherence to colonic mucins and colonization of the large intestine. Several risk factors, including immune microbial interactions, genetic susceptibility and malnutrition, can predispose individuals to severe disease [Amoebic dysentery is a common health condition throughout the developing world. In Mexico, still ranks among the 20 most common causes of death . Accordi disease , 4. Clin disease .The novel Coronavirus Infectious Disease 2019 (COVID-19) caused by SARS-CoV-2 is known to preferentially infect the cells of the respiratory system; however, recent studies suggest the virus has an affinity for other organs, suggesting that ‘organotropism influences the course of COVID-19 disease and, possibly, aggravates pre-existing conditions’ . The preA 54-year-old male with a 2-year history of hypertension presented to the ER with dyspnea, anosmia and dysgeusia. Oxygen saturation (SatO2) was 62%, blood pressure (BP) was 149/100 mmHg and temperature was 35.6°. A detailed lab analysis is shown in The combined presentation of hematochezia and elevated D-dimer levels in the setting of amoebic colitis and COVID-19 makes this an unusually challenging clinical encounter and surgical case. Typically, patients with extensive ulcerations disposed to heavy blood loss can have a favorable outcome in the operating room if infection is avoided. What makes this case uniquely intriguing is the concomitant interplay of immunological events characterized by both illnesses. It is highly probable that the pathological conditions of this gentleman’s pre-existing amoebic colitis were aggravated by SARS-CoV-2 infection.E. histolytica initiates once trophozoites adhere to colonic epithelial cells, via the Gal-/GalNAc-specific lectin, whereby a lateral invasion gives rise to the classic flask-shaped ulcerations of amebiasis. After adhesion, receptors (TLR2/TLR4) expressed in the surface of both intestinal epithelial cells and resident macrophages recognize the carbohydrate domain of the lectin and induce the canonical pathway for inflammation [E. histolytica have been implicated in triggering an inflammatory response in the gut and evasion of immunological mechanisms [The induction of tissue damage in ammation , includiammation , involveammation , 9. Apprchanisms , 11, limEmerging evidence of isolated SARS-CoV-2 from fecal samples suggests an enteric involvement resulting in GI symptoms prevalent in 17.6–61% of patients . The expIn cases of severe COVID-19, a significant elevation of IL-6 and D-dimers was associated with sepsis, coagulopathies and increased mortality .In our case, it is complicated to determine to what extent SARS-CoV-2 infection was a trigger for associated coagulopathies, and this dilemma materialized in the contraindication of corticosteroids for intestinal amebiasis due to increased incidence of perforation in intestinal lesions . NeverthE. histolytica infection. It is our purpose that this report can be used as an example to better inform surgical teams who are facing the unprecedented demands of this global pandemic since the underlying conditions diagnosed with SARS-CoV-2 may represent a veritable challenge for the patient’s treatment plans. We are optimistic that the scientific and medical communities can proactively advance the development of future solutions and perioperative protocols targeted to aid the most vulnerable patients in developing countries.This case report represents a considerable gap in the knowledge of gut mucosal immunity, eliciting distinctive inflammatory profiles in an organ dependent manner and further complicating a pre-existing condition, namely


A growing number of studies indicate that exposure to social stress, such as perceived racial discrimination, may contribute to poor health, health behaviors, and health disparities. Increased physical activity (PA) may buffer the impact of social stress resulting from racial discrimination. However, to date, data on the relationship between racial discrimination and PA have been mixed. Part of the reason is that the effect of perceived racial discrimination on PA has primarily been examined in cross-sectional studies that captured retrospective measures of perceived racial discrimination associated with individuals’ current PA outcomes. The association between real-time perceived racial discrimination and PA among African Americans remains unclear.The purpose of this study is to examine the relationship among demographic, anthropometric and clinical, and psychological factors with lifetime racial discrimination and examine the within- and between-person associations between daily real-time racial discrimination and PA outcomes  measured by ecological momentary assessment (EMA) and accelerometers in healthy African Americans.This pilot study used an intensive, observational, case-crossover design of African Americans (n=12) recruited from the community. After participants completed baseline surveys, they were asked to wear an accelerometer for 7 days to measure their PA levels. EMA was sent to participants 5 times per day for 7 days to assess daily real-time racial discrimination. Multilevel models were used to examine the within- and between-person associations of daily racial discrimination on PA.r=0.75; P=.02). Daily EMA-reported microaggression was associated with depressive symptoms , past race-related events , and lifetime discrimination . In the within-person analyses, the day-level association of racial discrimination and sedentary time was significant , indicating that on occasions when participants reported more racial discrimination than usual, more sedentary time was observed. Between-person associations of racial discrimination  or microaggression  with total energy expenditure were suggestive but inconclusive.More EMA-reported daily racial discrimination was associated with younger age (Concurrent use of EMA and accelerometers is a feasible method to examine the relationship between racial discrimination and PA in real time. Examining daily processes at the within-person level has the potential to elucidate the mechanisms of which racial discrimination may have on health and health behaviors and to guide the development of personalized interventions for increasing PA in racial ethnic minorities. Future studies with a precision health approach, incorporating within- and between-person associations, are warranted to further elucidate the effects of racial discrimination and PA.RR2-10.1002/nur.22068 African Americans continue to experience disproportionately higher rates of cardiovascular disease and metabolic disorders than their White counterparts . AlthougSocial stress derived from systems of inequality, such as racial discrimination, may provoke severe psychological and physiological responses and has been associated with unhealthy behaviors ,7. StudiIncreased physical activity (PA) may buffer the impact of social stress resulting from racial discrimination ,10. To dIn addition, although not in the context of racial discrimination, some studies of psychological stress in other populations have linked perceived stress with less PA ,14. In rTo date, data on the relationship between racial discrimination and PA are sparse and inconsistent. Part of the reason is that the literature to date on the effect of perceived racial discrimination on PA comprises mostly cross-sectional studies that capture retrospective measures of lifetime discrimination associated with individuals’ current health outcomes. Such data may be subject to recall and rumination biases. Furthermore, racial microaggressions—the brief and commonplace daily verbal or nonverbal denigrating messages directed toward racial and ethnic minorities that carry the offending party’s implicit or unconscious bias—have been shown to disempower racial minorities and may negatively impact health outcomes ,18. HoweEcological momentary assessment (EMA) is a real-time, self-report data-capturing method in which people report behavior in real time at multiple time points in their natural environment. It may reduce recall biases and enhance ecological validity by collecting self-report data that are more proximal to the time and place  in which stressful events and behaviors occur . RecentlTherefore, the purpose of this pilot study is (1) to describe the relationship among demographic , anthropometric and clinical factors , and psychological factors (depression) with lifetime racial discrimination and (2) to examine the effects of real-time racial discrimination on total energy expenditure, sedentary time, and moderate-to-vigorous physical activity (MVPA) patterns of objectively measured PA using accelerometers and a real-time data capture strategy, that is, EMA in healthy African American adults at both the group  and individual  level.This study is a substudy of an intensive, observational, case-crossover design to examine the effects of perceived racial discrimination on physiological  and behavioral responses in African Americans. Details of the overall study protocols have been published elsewhere . In a caBuilding on a relationship developed over the past 10 years, the research team recruited participants from greater New Haven communities in Connecticut via flyers and word-of-mouth communication within African American communities. Before implementing the study, we held meetings with community stakeholders to discuss an effective recruitment plan and the details of the pilot study protocols. Potential participants were called in and were screened by phone and scheduled for a baseline orientation visit. The inclusion criteria were (1) self-reported African American or Black, (2) aged between 30 and 55 years, (3) currently employed, (4) ownership of a smartphone, (5) able to respond to smartphone-based random survey prompts  at least 3 times per day, and (6) English speaking. We excluded participants who were pregnant or who had serious acute or terminal medical conditions that would preclude PA. The sample size (n=12) was largely based on guidelines for pilot studies that suggest 10 to 40 participants per cell . Even asBaseline surveys included sociodemographic characteristics; current smoking status (yes or no); and alcohol consumption by the Alcohol Use Disorders Identification Test , which iMajor Life Discrimination (MLD) scale is a 9-item self-report measure of past exposures to lifetime discrimination in diverse domains. Respondents indicated whether they had ever experienced each listed major discrimination event  [Race-Related Events Scale (RES) has 22 items to assess exposure to stressful and potentially traumatizing experiences of race-related stresses in adults. Respondents indicated whether they had ever experienced each event (yes or no), and the items were summed for a total RES score ranging from 0 to 22 (Cronbach α=.78-.88) [Perceived racial discrimination was measured at baseline using 2 scales. The h α≥.88) . The MLD.78-.88) . Higher The Black Racial Identity–Centrality subscale (Cronbach α>.77) is an 8-item, 7-point Likert scale (ranging from strongly disagree=1 to strongly agree=7). The centrality dimension of racial identity refers to the extent to which individuals normally define themselves with regard to race. It is a measure of whether race is a core part of an individual’s self-concept . After rsubjective social status, participants were asked to place an “X” on the rung that best represented where they thought they stood on the ladder, with 10 rungs described as follows: at the top of the ladder are people who are the best off, those who have the most money, those who have the most education, and those who have the best jobs, and at the bottom are people who are the worst off, those who have the least money, those who have the least education, and those who have the worst jobs or no job  [For  ρ=0.62) ,33.The Center for Epidemiological Studies Depression Scale (CES-D) is a 4-point Likert scale that captures current depressive symptoms with 20 items on how respondents have felt or behaved during the past week by selecting 1 of the 4 options . The items were summed to obtain a total score. Higher numbers indicate greater depressive symptoms (Cronbach α>.85) . A recenPerceived racial discrimination was measured using the Experiences of Discrimination   and RaciPA was measured using a triaxial hip accelerometer (ActiGraph GT9X), which samples movement at 30 Hz and aggregates data into 60-second epochs. The intensity cut points for PA were defined using validated thresholds for vertical axis accelerometry  . Energy 2). Percent body composition was measured using the same digital scale that measures foot-to-foot bioelectric impedance. This method has demonstrated significant correlations with the gold standard of body fat calculation  [Institutional review board approval was obtained from Yale University, and written informed consent was obtained from all participants. At the initial study visit, face-to-face baseline interviews were completed using validated questionnaires. Body weight and height were measured using a portable electronic scale  and a stadiometer (Seca) following standard procedures. BMI was calculated as weight (kg)/height squared (mry scan) . After 5To tailor the EMA survey delivery time, we asked participants for their sleep, wake, or commuting schedules by phone before the baseline study visit. At the baseline visit, we loaded the mEMA app, which is compatible with both iOS and Android operating systems, into each participant’s smartphone. The EMA survey prompted each participant at a random time within the 5 preprogrammed windows daily  for 7 days  to ensure adequate spacing throughout the day, except for nighttime and commuting time. Upon hearing the signal or vibration, the participants were instructed to complete a short electronic question sequence using their smartphone. Each EMA survey took approximately 3-4 minutes to answer. The EMA data collection system recorded the date and time it took each participant to respond to a random prompt survey and the date and time the survey expired. The survey expired after 40 minutes of nonresponse. After no entry was made, the EMA program became inaccessible until the next recording opportunity.Participants were instructed to wear an accelerometer on their right hip during waking hours for 7 consecutive days to obtain at least three weekdays and one weekend day to determine the daily variability ,43. A paEMA data were exported from the mEMA server to a comma-separated values file format. We entered the EMA and accelerometer data as well as the baseline surveys and anthropometric and clinical data into a database uploaded into SAS for analysis. We reviewed the data and corrected errors, missing data, outliers, and skewness and calculated the scale scores for the EMA responses. Descriptive analysis was used for demographic characteristics, anthropometric and clinical data, and the average values for EMA and PA data. Pearson and Spearman correlation coefficients were calculated at the individual level using the following variables: age, sex, BMI, CES-D, RES sum, MLD sum, annual income, education, blood pressure, body fat, racial identity, subjective social status, smoking and alcohol consumption, EMA survey data, and accelerometer data. EMA and PA data were scored for daily and individual (average in subject) levels. Intraclass correlation coefficients were calculated to quantify the proportions of total variance of PA explained by within- and between-person variances. Multilevel models for predicting PA (percentage sedentary time and percentage MVPA) were developed to examine the associations with EMA survey data  at the 2-hour interval (within-person), daily (within-person), and individual (between-person) levels. The models included within- and between-person levels of racial discrimination (model 1) or microaggression (model 2) with covariates . Compound symmetry was used as a within-person correlation structure. Standardized coefficients were obtained using standardized outcomes and covariates with 0 mean and 1 SD.The mean response rate for EMA surveys was 83% , and the mean number of EMA responses per day was 4.0 (SD 1.2) out of a possible maximum of 5 per day. A total of 83.3% (10/12) of participants met the inclusion requirements for valid accelerometer data (≥10 hours/day wear time) and wore the accelerometer on the hip 6 out of 7 days. The mean EMA-reported daily racial discrimination was 0.61 (SD 0.85) per day, with a range of 0-2.28 (possible range: 0 to 10 times/day). Three participants reported no daily racial discrimination over the 7-day period . For the EMA-reported daily microaggression, the mean score was 50.26 (SD 18.11), with a range of 19.14-76.71 (possible range: 15-105/day).2; approximately 42% (5/12) of the participants were obese. The mean MVPA was 18.5 minutes/day, and the mean sedentary time was 8.6 hours/day. Paired data, including both EMA and valid accelerometer data, resulted in a sample size of 9.Participant characteristics and descriptive statistics from the survey and anthropometric and clinical and accelerometer data are presented in r=0.58; P=.04) and a higher frequency of major lifetime discrimination . Visceral fat was associated with diastolic blood pressure  and sedentary time  but was not associated with major lifetime discrimination. Income level was not significantly associated with Black racial identity .In the bivariate analysis, using baseline surveys and anthropometric and clinical data, depressive symptoms were associated with major lifetime discrimination . Black racial identity was not significantly associated with EMA-reported daily racial discrimination  or microaggression . Daily EMA-reported microaggression was associated with depressive symptoms , past race-related events , and major lifetime discrimination . A higher total energy expenditure was significantly associated with less major lifetime discrimination . Less sedentary time was significantly associated with a stronger Black racial identity . More MVPA was significantly associated with lower levels of subjective social status .Intraclass correlation coefficients were calculated to represent the proportion of the total variance of the PA outcomes explained by the between-person levels. They were 0.54, 0.26, and 0.66 for total energy expenditure, sedentary time, and MVPA, respectively.P=.18) and slightly more MVPA . Similarly, during the 2-hour windows in which they reported more perceived microaggression, they had less sedentary time  and less MVPA . However, none of these relationships during the 2-hour windows reached statistical significance.The within-person interval-level analysis found that during the 2-hour windows in which people reported more perceived racial discrimination, they had moderately greater sedentary time , indicating that during days when participants reported more perceived racial discrimination, they had moderately more sedentary time.The within-person daily levels and between-person analyses are presented in Perceived racial discrimination is a significant psychological stressor that is hypothesized to have negative mental and physical health consequences with potential interactions with unhealthy behaviors. The relationship between overall psychological stress level and PA using EMA and objective measures has been evaluated in the general population; however, in what we believe to be the first published study of its kind, we examined momentary- and daily-level perceived racial discrimination and PA levels using EMA and accelerometers in African Americans. We collected repeated real-time racial discrimination exposure data in the natural environment while simultaneously collecting objective measures of sedentary behaviors and PA among African Americans. We also demonstrated the utility and feasibility of EMA coupled with accelerometers in studying the relationship between daily racial discrimination and PA in African Americans. Conventional accelerometer protocols require only 4 valid days for a 7-day wear period to be considered valid ,43. ApprIn the examination of within-person level data, on days when participants reported more perceived racial discrimination than usual , more sedentary time was observed in the accelerometer data. The between-person analysis did not duplicate this finding in our study. However, this is consistent with the findings of between-person analysis in a prior study examining the relationship between general psychological stress and sedentary behaviors in other populations: end-of-day general stress ratings were not associated with sedentary time in the between-person analysis (at the group level) . The infAn important advantage of the EMA methodology is its ability to examine the frequency of racial discrimination experiences in real time and assess the impact of the experiences in a microtemporal relationship . In our study, participants reported, on average, 0.61 overt racial discrimination experiences per day, and most participants experienced substantial daily microaggressions. The reported frequency of racial discrimination varies widely across studies -49. In eIn several studies of psychological stress, not specific to racial discrimination-related stress in the general population, episodic stress predicts less PA, more sedentary behaviors, and reduced total energy expenditure ,51. ConsConsistent with other studies ,53,54, rThis study had several limitations. Although we found similar trends in within- or between-person effects on sedentary behaviors and PA, compared with other studies of general psychological stress, our small sample size offers limited evidence supporting racial discrimination as an antecedent to sedentary behaviors or PA. EMA minimizes recall bias and errors. However, it is also possible that our study findings may have been influenced by vigilance to discrimination from the repetitive assessment involved in EMA. In addition, the high CES-D scores observed in our participants may have influenced the associations with perceived racial discrimination or PA. Although findings are mixed, previous studies have shown that neighborhood environments such as walkability, safety, or crime were associated with individuals’ PA levels in the general population ,58. We oDespite these limitations, this study provides valuable insights into examining the within-person effects of racial discrimination on health behaviors and suggests the need to examine a more complex relationship between racial discrimination and lifestyle behaviors with time-varying factors.just-in-time interventions [There is a growing emphasis on within-person examination of health behaviors and psychosocial correlates and on the importance of leveraging these data to develop personalized, ventions ,60. ExamIn conclusion, the results of this study highlight the utility and feasibility of a within-person approach to target reductions in sedentary time and improvements in PA associated with daily racial discrimination by using EMA and an objective measure of PA. Further studies are needed to confirm the observed findings in light of the limitations of this study, including its small sample size. A precision health approach that incorporates between-person associations and accounts for within-person variations in the relationship between racial discrimination and health behaviors is warranted to mitigate race-based health disparities.


This unique case highlights the electrophysiologic management and risk assessment of sudden cardiac death in a 35-year-old woman with a history of D-transposition of the great arteries status post–Mustard atrial switch repair. A 35-year-old woman with a history of D-transposition of the great arteries (d-TGA) status post–Mustard atrial switch surgical repair at six months of age presented for an electrophysiologic (EP) evaluation of palpitations. The patient had had an uncomplicated first pregnancy, yet in the postpartum state was diagnosed with atrial flutter (AFL) and atrial fibrillation (AF) requiring electrical cardioversion. Sotalol was initiated, then stopped due to gynecological bleeding, and the patient was subsequently maintained without medications.During her second pregnancy, the patient experienced recurrent palpitations and was diagnosed with AFL. She was again trialed on sotalol but did not tolerate the medication. Ultimately, she required direct current cardioversion during pregnancy, and the child was urgently delivered via cesarean section. Her adult congenital cardiology team planned for an EP study and ablation after her recovery, but the patient moved to California prior to the procedure. She presented as a new patient to an adult congenital EP clinic to establish care 12 months after her cardioversion and birth of her child with symptoms of palpitations. A five-day event monitor revealed sinus arrhythmia with sinus rates between 64 and 141 bpm, with rare multifocal ventricular ectopic beats [94 total premature ventricular contractions (PVCs)]; one supraventricular tachycardia (SVT) noted to be atrial tachycardia versus interpolated PVCs/nonsustained ventricular tachycardia (VT) of 10 beats at a maximum rate of 113 bpm; and sinus node dysfunction (SND) with three pauses, with the longest pause lasting 2.1 seconds. and 2, right and left heart catheterizations (RHC/LHC) showing both hemodynamics and a beautiful overlay of the d-TGA anatomy –6, an EP study  and 8, and also consideration of placement of a dual-chamber implantable cardioverter-defibrillator (ICD) . The differential diagnosis included SVT; sinus tachycardia; AFL; AF; atrioventricular (AV) nodal reentrant tachycardia (AVNRT); AV reentrant tachycardia; intra-atrial reentrant tachycardia (IART); paroxysmal atrial tachycardia, nonsustained VT; and frequent premature atrial, ventricular, or atrial/ventricular beats.The patient was referred to the University of California Irvine Medical Center for a comprehensive cardiac workup, including electrocardiograms On the day of the procedure, the patient was hemodynamically stable, with an unremarkable physical examination with no jugular venous distension, her lungs were clear to auscultation bilaterally, had a normal heart rate and rhythm with a 2/6 murmur at the left midsternal border, and no pitting edema was noted.Table 1. RHC/LHC findings can be found in Table 2.The patient’s echocardiography results can be found in . There was a line of block across the CTI from the PVA to the tricuspid valve. The ablation catheter was then placed in the venous sheath into the SVA and radiofrequency energy was applied to the proximal CTI to the IVC. Bidirectional CTI block was confirmed with pacing lateral and medial to the radiofrequency line. No further tachycardia was inducible at baseline or on isoproterenol.In this EP study, IART was induced with a cycle length of 300 ms with 2:1 AV conduction. Three-dimensional electroanatomic mapping was performed  utilizing a multipolar mapping catheter  in the systemic venous atrium (SVA) and an irrigated-tip radiofrequency catheter  positioned retrograde across the aortic valve into the RV and across the tricuspid valve into the pulmonary venous atrium (PVA). Entrainment was performed at the cavotricuspid isthmus (CTI) from the PVA and the SVA with a postpacing interval minus the tachycardia cycle length of less than 10 ms at each location, confirming the CTI-dependent IART. Radiofrequency energy applied to the CTI from the PVA resulted in the termination of the tachycardia . Interestingly, due to the atrial switch repair (Mustard) for d-TGA, the systemic venous anatomy diverts blood flow from the SVC to the native left atrium (LA) and subpulmonary LV. A 9-French (Fr) introducer was used, and a 9-Fr lead was threaded across the Mustard baffle into the LV apex. For the atrial lead, a 6-Fr lead was threaded through another 7-Fr sheath into the native LA appendage (LAA).In addition to the EP study, a transvenous dual-chamber ICD with atrial antitachycardia pacing capability was implanted in the left pectoral area The patient was discharged home the following morning and was followed up with at 10 days, two months, and four months after her procedure. She remains asymptomatic with no atrial arrhythmias and no ventricular arrhythmias, with 11.2% atrial pacing and no appropriate or inappropriate shocks.1 The natural history of d-transposition shows that, without treatment, the mortality rate is 30% in the first week, 50% in the first month, 70% at six months, and 90% in the first year without repair. The first surgical “corrective” procedure was an atrial septectomy performed by Dr. Alfred Blalock; his assistant, Vivien Thomas; and his resident at the time, Dr. C. Rollins Hanlon, at Johns Hopkins University Medical Center to allow for an effective mixing of parallel circulatory systems.2 Several years later, the atrial switch procedures, Senning first in 1957, then Mustard in 1963, revolutionized the surgical management of d-TGA, thereby improving the 10-year survival rate to 90%.2 The Mustard procedure employs a baffle to divert the caval blood to the anatomic LA and LV. This venous blood is then pumped to the lungs through the pulmonary arteries . This allows for the total correction of the d-TGA. Three years after the Mustard procedure was developed, Dr. William Rashkind developed a balloon septostomy, which was implemented in the first successful arterial switch in 1975 by Jatene et al. This increased the 10-year surgical survival rate to 97%.4d-TGA is the primary condition among 5% to 7% of all congenital heart defects seen.5 Other atrial tachyarrhythmias seen in this population include AVNRT, focal atrial tachycardia, and AF.5Notable postsurgical anatomical sequelae include baffle obstruction, systemic RV failure, and deconditioned subpulmonary LV. As surgical survival rates began to increase and more patients reached to adulthood, arrhythmias, primarily IART or AFL, became an increasingly well-recognized complication. It is thought that IART manifests from the multiple atrial suture line placed during surgical correction as well as reconstruction and scarring of the atrial tissue.6 Kanter et al. successfully conducted radiofrequency ablations of SVT substrates, including IART, in 11 patients with either Mustard (n = 9) or Senning (n = 2) operation.7 CTI-dependent flutter still remains the most common mechanism for IART in patients with atrial switch repairs for d-TGA. Importantly, because the baffle transects the CTI, ablation is required on both the systemic and pulmonary venous sides of the baffle in order to create a bidirectional conduction block across the entire CTI, as was required in our patient. One notable cause of death in these patients is premature sudden cardiac death (SCD). The incidence rate of this risk is 4.9 per 1,000 patient-years in SCD and 6.9 per 1,000 patient-years in non-SCD, with patients with d-TGA having a higher risk than those with tetralogy of Fallot in the Kaplan–Meier analysis for SCD-free survival.8 Interestingly, the presence of arrhythmic or heart failure symptoms in addition to documented AFL/AF was the highest predictor of SCD in patients with d-TGA , documented arrhythmia (OR: 3.47), SND (OR: 2.4), and AFL/AF (OR: 4.86).9 This patient had these risk factors for SCD and hence was offered a primary prevention ICD.Due to the arrhythmogenic potential seen in these patients, many preprocedural considerations should be taken into account, including venous access , AV node location, AV node access, coronary sinus access, CTI access, stable reference catheter, ventricular dysfunction, SVA, and PVA. Collins et al. demonstrated the location of ablation for IART in patients with congenital heart diseases, including after Mustard/Senning (n = 14 sites) and Fontan (n = 40 sites) procedures.10 β-blockers have shown to offer a protective effect against primary ventricular arrhythmias among d-TGA patients. d-TGA patients who could tolerate β-blockers experienced fewer appropriate shocks compared to patients who could not.10 Preprocedural considerations for ICD implantation include baffle obstruction, baffle leaks, thin LV and risk of perforation, defibrillation vector, and atrial lead position in LAA extraction.ICD placement in d-TGA patients is indicated for secondary prevention [hazard ratio (HR): 5.1], ventricular septal defect (HR: 4.3), moderate tricuspid regurgitation (HR: 4.1), corrected QT (HR: 1.02), and the inability to tolerate β-blockers (HR: 11.3).This unique case also highlights the EP management, arrhythmogenic potential, and risk of SCD in patients with prior atrial switch repair for d-TGA. It also highlights the comprehensive nature of treating IART in this subset of patients. This case demonstrates how multifaceted imaging and investigative modalities were used, including echocardiography, LHC, RHC, and EP studies, to grasp a better anatomical understanding needed to treat these arrhythmias while simultaneously assessing/reducing the risk of SCD.Our patient was seen postoperatively in the clinic and appeared to be doing well without recurrence of symptoms or significant arrhythmias noted on device interrogation and with excellent pacing and sensing parameters. The patient was seen again five weeks later without any complaints. ICD device counters were checked at each follow-up visit without any significant arrhythmia recurrences noted as of the most recent follow-up. She continues to be followed up with every two to three months on a regular basis for ICD interrogations and management.Atrial switch repair for d-TGA is an arrhythmogenic substrate. The risk of SCD is significant in d-TGA/atrial switch, and dysrhythmias are a risk factor for SCD. Successful EP management requires knowledge of the patient’s surgical/anatomical history and creativity.


The COVID-19 pandemic has resulted in unparalleled changes to patient care, including the suspension of cancer surgery. Concerns regarding COVID-19-related risks to patients and healthcare workers with the re-introduction of major complex minimally invasive and open surgery have been raised. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (EG) surgery.This was an international, multi-centre, observational study of consecutive patients treated by open and minimally invasive oesophagectomy and gastrectomy for malignant or benign disease. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 between 1 May and 1 July 2020. The primary endpoint was 30-day COVID-19-related mortality. All staff involved in the operative care of patients were invited to complete a health-related survey to assess the incidence of COVID-19 in this group.In total, 158 patients were included in the study . Overall, 87 patients (57%) underwent MIS . A total of 403 staff were eligible for inclusion, of whom 313 (78%) completed the health survey. Approaches to mitigate against the risks of COVID-19 for patients and staff varied amongst centres. No patients developed COVID-19 in the post-operative period. Two healthcare workers developed self-limiting COVID-19.Precautions to minimise the risk of COVID-19 infection have enabled the safe re-introduction of minimally invasive and open EG surgery for both patients and staff. Further studies are necessary to determine the minimum requirements for mitigations against COVID-19.The online version contains supplementary material available at (10.1245/s10434-021-09885-0) contains supplementary material, which is available to authorized users. The COVID-19 pandemic has seen unprecedented changes to the provision of healthcare so that services can focus their efforts on managing the crisis. Due to significant concerns pertaining to the safety of surgery and the associated increased morbidity and mortality, many elective operative programmes were suspended.Despite significant improvements in approaches to peri-operative care over the last decade, surgery for oesophago-gastric (EG) cancer is still associated with significant morbidity.Proponents of MIS argue that these risks are not evidence based and can be easily mitigated with the use of adequate personal protective equipment (PPE). Whilst healthcare services have been keen to ensure that adequate PPE is available for staff, it is not known what the minimum necessary requirements for PPE are in the context of COVID-19. Furthermore, in centres where the provision of MIS was commonplace, suspending these approaches may be exposing patients to wound and respiratory complications, which would result in longer lengths of stay in hospital. This would be particularly disadvantageous at a time where the risk of contracting COVID-19 in hospital may be significant.9To determine current practice with respect to mitigations aimed at reducing the risks of COVID-19 amongst patients undergoing EG surgery and healthcare workers involved in their care.In the context of these mitigations, to determine the incidence of COVID-19 and non-COVID-19 morbidity and mortality in both MIS and open surgery for EG cancer surgery.In the context of these mitigations, to determine the risk of ‘patient-to-staff’ transmission of COVID-19 amongst healthcare workers involved in the operative care of EG surgical patients.This study aims to assess, in the context of significant regional levels of COVID-19, the safety of re-introducing MIS and open surgery for EG disease, both from the perspective of the patient and healthcare workers. The objectives are as follows:This was an international, multi-centre, observational study of patients who were scheduled for elective minimally invasive or open oesophagectomy or gastrectomy. To assess the potential risk to healthcare workers of undertaking these procedures, all staff members who were present in theatre at the time of surgery were asked to complete an anonymous COVID-related health questionnaire.Participant data were collected from nine specialist European centres for EG surgery. Each centre served patients from populations that had been particularly affected by the COVID-19 pandemic from the perspective of infections and deaths .Aged 18 years and overProcedure: oesophagectomy or gastrectomy Pathology: malignant and benign diseaseOperative approach: totally minimally invasive, hybrid minimally invasive or totally open surgeryConsecutive patients who had undergone EG surgery between the 1 May 2020 and the 1 July 2020 at each centre were included. Patients were followed up for a minimum of 30 days. The following eligibility criteria for patients were applied:All healthcare workers involved in the care of the patient within the operating theatre were invited to complete an anonymous health survey (Supplementary Appendix 1). This group was the focus of our survey as they were deemed at particular risk from potential ‘patient-to-staff transmission’ due to their involvement in aerosol generating procedures . Local collaborators completed a register of eligible staff members during each case to ensure all eligible healthcare workers could be contacted to complete the survey. This non-validated questionnaire was developed by the study team with the objective of identifying the incidence of COVID-19 in medical staff involved in the care of included patients. Surveys were sent out after 15 July 2020  to accommodate for a COVID-19 incubation period of up to 2 weeks.Laboratory testing for COVID-19 was based on viral RNA detection by quantitative reverse transcription polymerase chain reaction (RT-PCR). Sampling, including nasopharyngeal swabs and bronchoalveolar lavage, and analyses were undertaken according to local hospital protocols. RT-PCR testing was available in all participating centres. Oesophagectomy included both two- (intra-thoracic anastomosis) and three-stage  approaches. Totally minimally invasive oesophagectomy (tMIE) was defined as surgery using laparoscopic and thoracoscopic techniques, with hybrid minimally invasive oesophagectomy (hMIE) defined as surgery using a laparoscopic approach with open thoracotomy. Both total and partial gastrectomy requiring alimentary reconstruction were included, however, wedge excision of gastric lesions was excluded from analysis.Data were collected prospectively by each local collaborating team using a standardised Microsoft Excel spreadsheet. Patient demographics , disease data , COVID-19-related variables (previous RT-PCR testing and results) and operative approach were collected for each case.https://www.ecdc.europa.eu/) were collected to describe COVID-19-related hospital and intensive care unit occupancy and death before and during the study period.Participating centres were also asked to describe local precautions employed to reduce the risk of COVID-19 to both patients and staff . In addition, data from the European Centre for Disease Prevention and Control (www.esodata.org and www.gastrodata.org) in the field of EG surgery.The primary patient outcome was 30-day COVID-19-related mortality (confirmed by RT-PCR test) with the day of surgery defined as day 0. Secondary outcomes were COVID-19 infection (confirmed by RT-PCR test), non-COVID-19-related respiratory complications and other complications as defined by established international guidelines (A sample size was not applicable to this study. Whilst recruiting centres were defined as ‘high volume’ in comparison with others across Europe (at least 50–100 major EG cases per annum), it was necessary to balance this against the likely lower operative volumes as a result of the pandemic. Our aim was to produce relevant and externally valid evidence within a relatively short period of time, and so a pragmatic target of at least 100 eligible cases was set by the study management team.Only routine, anonymised patient data were collected with no change to clinical pathways.https://www.R-project.org/).Descriptive statistics were used to report participant characteristics and outcomes in this study including mean, standard deviation and 95% confidence intervals where appropriate. Patients outcomes were grouped according to surgery type (oesophagectomy or gastrectomy) and operative approach . Hybrid minimally invasive oesophagectomy (e.g. laparoscopic abdomen and open thoracotomy) was included in the minimally invasive group. Statistical analyses of the present study were performed using the R statistical package , with one centre not adopting a routine pre-operative testing policy at the time of the study. A total of 2 of the 149 tested (1.3%) were found to be positive for COVID-19, resulting in the postponement of their surgery. One patient tested negative 2 weeks later, whilst the other required multiple tests over the course of 6 weeks before a negative COVID-19 test was achieved. Both proceeded with surgery with curative intent as planned.With respect to the primary outcome, 39 (24.7%) patients underwent post-operative RT-PCR testing for suspected COVID-19 infections, of which none were positive. One death was reported (0.6%), which was ascribed to respiratory failure following open total gastrectomy in a patient whose post-operative RT-PCR test for COVID-19 was negative. Median length of stay in hospital was 10 days , with 153 (97.5%) being discharged home, and the remaining 4 (2.5%) to an intermediate care facility.Of the 403 healthcare workers eligible for inclusion into this study, 313 (77.7%) completed the COVID-19-related health survey  COVID-19 during the study period. Further study is urgently needed to understand the minimum precautionary measures required to ensure patients and staff remain safe.Supplementary material 1 (DOCX 21 kb)Below is the link to the electronic supplementary material.


The levels of urinary incontinence (UI) at adjuvant/salvage radiotherapy (ART/SRT) start strongly influence long-term UI recovery, possibly inducing clinicians to postpone radiotherapy “as much as possible” in order to maximize UI recovery, but possibly reducing radiotherapy efficacy. Our study analyzed UI recovery from prostatectomy to ART/SRT by means of the International Consultation on Incontinence Questionnaire-Short Form filled-in by patients at ART/SRT start. Three endpoints were investigated: frequency and amount of urine loss and the “subjective” patient-perceived detrimental impact on quality of life, as well as the possible influence of clinical and personality variables. The time elapsed from prostatectomy to radiotherapy start was the strongest predictor for each UI endpoint, all improving between four and eight months after prostatectomy, but without any additional long-term recovery.p-values ≤ 0.001); all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency. Conclusions: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI.Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it “as much as possible”, maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start. Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study  aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss , “objective” UI (ICIQ3 + 4), “subjective” UI (ICIQ5), and “TOTAL” UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression. Results: TTRT was the strongest predictor for all endpoints ( Adjuvant radiotherapy (ART) was believed to reduce the risk of recurrence after radical prostatectomy (RP) in patients with aggressive prostate cancer (PCa). However, three recently published non-inferiority phase III trials , as well as the ARTISTIC meta-analysis, clearly indicated that salvage radiotherapy (SRT) at the time of recurrence may now be regarded as a preferred option in the large majority of patients ,3,4.Immediate ART could theoretically still be considered a valuable option in the presence of few pathological pejorative findings such as positive surgical margins and/or lymph-nodal metastases: according to the ARTISTIC meta-analysis, owing to the low overall event rate, the power of the patient subgroup analyses indicating no superiority of ART when compared to early SRT, and also in the subset of men with positive surgical margins, was limited . SimilarA strong argument favoring SRT is the common belief that postponing post-prostatectomy irradiation until a better level of urinary incontinence (UI) has been achieved may result in a reduced risk of long-term radiotherapy-induced impairment of UI recovery . This isIn 2016, Tendulkiar et al. elegantly highlighted an inverse relationship between pre-SRT baseline PSA and the risk of distant metastases and death following SRT, with men receiving SRT at PSA levels ranging from 0.01 to 0.20 ng/mL exhibiting better oncological outcome across all Gleason score subgroups , in agren = 408) of patients treated with post-prostatectomy ART or SRT.Starting from these two assumptions, we sought to analyze the trend of UI recovery from RP to post-prostatectomy radiotherapy in a large cohort  identifier #NCT02803086) started in January 2014 with the goal of developing predictive models of hematological [The multi-Institutional IHU-WPRT TOX study  ,22. BothAccording to the protocol requirements, the validated Italian version of the ICIQ-SF questionnaire   is to beThe sum of the two scores, ICIQ3 + ICIQ4, pertains to the “objective” (OBJ) component of UI. Question 5  pertains to the subjective (SUBJ) patient-perceived impairment of quality of life attributable to UI. The total score  ranging from 0 (best) to 21 (worst), therefore comprises both an “objective” and a “subjective” component. It is rather intuitive that QoL impairment deriving from similar frequency and amount of urine loss may be perceived differently by patients, and therefore all of the three distinct aspects of radiation-induced urinary incontinence, OBJ, SUBJ, and TOTAL will be separately analyzed in the present analysis.Patient personality and its impact on UI were considered by means of the abbreviated 24-item version of the revised Eysenck personality questionnaire (EPQ-R) [n = 179, 44%) or SRT : 103 were from the pilot study [This analysis pertains to the first 408 patients treated with ART daily frequency: ICIQ3 > 2(b)amount of urine loss: ICIQ4 > 2(c)subjective: ICIQ5 > 4(d)objective: ICIQ3 + ICIQ4 > 5(e)total: ICIQ3 + ICIQ4 + ICIQ5 > 8The ICIQ based endpoints were selected following, as a reference, a previous analysis on UI in the radical setting  and evalnls function implemented in the R package stats. Coefficient estimation was based on an iterative process, which entails a linearization approximation leading to a least-squares problem at each step.First, the relationship between UI at radiotherapy and the time elapsed between prostatectomy and radiotherapy  was investigated. The scatter plot of each ICIQ-based score versus TTRT was represented. Data were grouped into deciles with respect to the distribution along the TTRT axis: mean values and their standard errors were considered to be representative of each decile interval. Points were fitted by a sigmoid curve with initial parameters manually selected and then optimized by the Subsequently, the best cut-off values for the TTRT, which best discriminate the highest risk of experiencing each of the five previously defined endpoints were identified by means of ROC curve analyses.The possible correlation between clinical and EPQ-R variables see  with eacn = 23). For 46 patients, the EPQ-R questionnaire was not available owing to patient refusal or largely incomplete forms.Mean imputation was performed for EPQ-R variables when only one answer for each personality trait was missing  logistic regression model. Each model was then reprocessed using only the variables retained by the MVA model with a p-value threshold ≤ 0.1. The multivariable analyses were subsequently repeated, excluding the personality variables.Variables with a 2). Internal validation was performed by 1000 bootstrap resampling: the Brier scores after bootstrapping were considered with and without optimism taken into account. Analyses were performed with MedCalc® version 12.1.4.0  and the R software version 3.2.4 .Goodness of fit was assessed by means of the Hosmer and Lemeshow test (H&L) and the calibration of the models evaluated through the calibration plot  at post-prostatectomy radiotherapy start were analyzed with the same procedure followed for the identification of the predictors of the five above described UI endpoints.The relationships between TTRT and the different ICIQ scores are plotted in p-values, and the best cut-off values are listed in All figures show an initial post-surgical plateau of the different UI aspects followed by a partial recovery and then by a new and definitive plateau. The most informative cut-offs in terms of TTRT with respect to the five previously defined UI endpoints ranged from 6.7 to 7.8 months. The coefficients of the sigmoid curves, the corresponding p-value always ≤ 0.001). With respect to the clinical variables, the p-values for androgen deprivation therapy, pathologic T-stage, and pre-RP PSA were always <0.1 with the sole exception of the SUBJ endpoint, while, with respect to the role of patient personality, neuroticism always emerged as a significant factor, unlike the other three personality traits. Of note, no correlation between the type of surgery and any of the considered endpoints was observed .The results of the univariate logistic regression are shown in The resulting multivariate models, shown in Interestingly, neuroticism was confirmed as an independent predictor of SUBJ and TOTAL UI as well as, quite unexpectedly, of daily frequency.2 ranging from 0.63 to 0.84. All calibration plots are shown in The goodness of fits were always satisfactory (H&L >0.05 and Brier score <0.216). For the models including more than one variable, the calibration showed excellent performance, with slopes ranging from 0.95 to 1.11, and with RThe corresponding models obtained excluding the EPQ-R variables are shown in 2 = 0.837). These results were confirmed even after having excluded the role of personality  finding was that no further significant improvement of pre-radiotherapy baseline UI was recorded beyond 7–8 months after prostatectomy.As pre-radiotherapy baseline UI was expected to be the strongest predictor of post-irradiation late UI ,25,26, tIf further confirmed, these findings could lead to a dramatic reduction in the current, apparently unbridgeable, gulf between ART and early SRT.No significant differences in terms of UI were observed among patients managed with different surgical approaches, as already noted ,28,29. NInterestingly, one-fourth of the patients included in this analysis were completely dry at the start of post-prostatectomy radiotherapy, representing undeniable proof of the significant improvement in the surgical management of prostate cancer. The complete recovery from UI before post-prostatectomy radiotherapy was, as expected, more frequent in younger patients and strongly related to TTRT (>7 months). Nevertheless, the rate of the completely dry patients (which significantly increased up to 40% in patients who started radiotherapy ten months after surgery), permanently plateaued, even when several years had elapsed from surgery; clearly indicating that waiting more than ten months after prostatectomy does not further increase the likelihood of starting radiotherapy in a “completely dry” condition.As a final remark, higher levels of neuroticism, i.e., emotional instability, nervousness, and general anxiety, were associated with a reduced capacity to cope with UI, leading to an increased perception of impaired QoL deriving from UI, but also to a possible overestimation of daily frequency (ICIQ3 score >2, OR 1.18, Excluding the personality-related variables, an independent role of age in increasing the risk of UI , as alreAn important limitation of the current analysis, based on a prospective study originally aimed at investigating the predictors of acute and late radiation-induced toxicities, is the lack of any pre-surgical assessment of urinary functionality as well as the lack of information regarding perineal re-education and medications for urinary frequency after surgery.Both objective and subjective UI improved notably in the first 7–8 months after RP in candidates for post-prostatectomy radiotherapy, but with no further significant recovery for longer periods after surgery.Higher levels of neuroticism may lead to some overestimation of UI.


Background: Fear of flying (FoF) is a phobia with 10–40% prevalence in the industrialized world. FoF is accompanied by severe economic, social, vocational, and emotional consequences. In recent years, virtual reality (VR)-based exposure therapy (VRET) for FoF has been introduced. Positive long-term efficacy of FoF-VRET has been reported by several studies, which, however, were limited by relatively small, non-representative samples and a lack of comparative pre/post functional efficacy outcome measures. Our objective was to evaluate the efficacy of a VRET treatment utilizing a large-scale VR system, experienced by a representative sample of self-referred individuals.Methods: We conducted a retrospective survey. Of 274 individuals who received the treatment (over a period of 3 years), 209 met inclusion/criteria, and 98 agreed to participate. We mainly collected information regarding flight activity before and after treatment relying on evidence such as boarding passes and flight tickets. The primary outcome measures were (1) number of flights per month (FpM) and (2) number of flight hours per month (FHpM). For each participant, these outcomes were computed for the post-treatment period (≥6 months after FoF-VRET) and the corresponding pre-treatment period.Results: FpM (mean ± SD) increased from 0.04 ± 0.06 to 0.16 ± 14 flights (p < 0.0001). FHpM rose from 0.19 ± 0.35 to 0.79 ± 0.87 h per month (p < 0.0001).Conclusion: These results are indicative of FoF-VRET treatment efficacy. Future studies should evaluate long-term maintenance of the treatment effect and thus identify the optimal frequency for delivery of periodic booster treatments. Airplanes are the safest, most common way to travel for long distance trips in the industrialized world . Fear ofSeveral pharmacological treatments exist for FoF including anti-anxiety medications like benzodiazepines . Other tOver the last decade, virtual reality (VR) has become a viable method for administering exposure therapy for anxiety disorders. For example, several VR-based exposure treatments for post-traumatic stress disorder have been proposed  in the prevalence of (voluntary) flying in the period following the conclusion of VRET treatment . FurtherMethods). The FoF-VRET is provided as a personalized, flexible treatment; there are a number of variations that the therapist can apply to the treatment at his/her discretion in accord with professional experience. Until January 2019, more than 274 individuals have been treated.The research Center of Advanced Technologies in Rehabilitation (CATR) at Sheba Medical Center  has developed a FoF-VRET using a large-scale VR system . Among the benefits of this methodology are reduced bias associated with willingness to participate in experimental research, reduced bias associated with an onsite office interview by a clinician, and reduced “gratitude effect” consequent to pro bono research participation since participants in the present study paid out-of-pocket to obtain a clinical service.The Inclusion criteria were completion of the FoF-VRET treatment regimen at the clinical virtual reality facilities in the virtual reality facilities of the rehabilitation hospital at Sheba Medical Center and having an email address on file . The Exclusion criteria were non-responsive to email, refusal to participate or <6 months after treatment completion.Six months was set as the minimum time from treatment completion to allow a reasonable amount of time for participants to fly and for comparability to the literature (see section “Main Outcome Measures”). Of the 209 individuals we contacted, 98 actually participated. Individuals were excluded for the following reasons: 50 were non-responsive, 53 refused to participate, and eight were questioned <6 months from treatment completion. The majority of the participants were female (54%); mean age ± SD was 43.9 ± 13.3, and the range was 17–77 years. For technical reasons, age was not available for 15 participants, and gender was unavailable from one participant.First, potential participants were emailed for their consent to participate; those who agreed were then contacted by phone to confirm their informed consent. Next, a structured phone interview was conducted. The interview consisted of three parts:Confirmation of FoF-VRET treatment dates and recording the reason or reasons for self-referral.Information on flight activity for the period following treatment completion and a corresponding period of identical length of time prior to treatment initiation. For each flight, participants reported their destination and flight duration. For verification purposes, participants were asked to furnish supporting material including boarding passes and passport stamps.Questions about the FoF-VRET treatment experience, including whether they underwent other FoF treatments ±1 year before/after the FoF-VRET treatments.The primary measure of FoF-VRET efficacy was number of flights per month (FpM). The secondary outcome measure was number of flight hours per month (FHpM). For example, a participant interviewed 18 months after VRET completion reported the following flight information: to New York (11 h) in month +2, to London (5.5 h) in month +7, and to Eilat (1 h) in month +17. His/her outcome measures were thus FpM = (3/18) and FHpM = (17.5/18). Corresponding pre-treatment measures were calculated from data for the identical period of pre-treatment time.Refer to the p < 0.05). Alpha level was set at p < 0.05, two-tailed.Non-parametric within-participant analyses (Wilcoxon signed-rank tests) were used to compare pre- and post-treatment FpM and FHpM levels as Kolmogorov-Smirnov tests indicated that these outcome measures do not follow a normal distribution .Regarding flight activity outcomes before and after treatment, within-participant analyses revealed a significant difference for FpM and FHpM before  and after  treatment  and “other treatment” groups. For each participant, we computed pre/post change  in FpM and FHpM, respectively. Man-Whitney tests revealed no significant differences between the groups , suggesting that other treatments did not appreciably affect the increased flight activity we attribute to FoF-VRET.To confirm that our findings regarding FoF-VRET efficacy were not unduly affected by the additional treatments, we conducted a This study aimed to determine the efficacy of FoF-VRET treatment using a retrospective follow-up questionnaire conducted over the phone. Our study is novel in that we evaluated individuals who voluntarily paid for and received treatment in our virtual reality center.This FoF-VRET has several advantages over standard FoF exposure treatments. Firstly, it provides a safe, controlled environment that can be continuously monitored and manipulated by professional therapists and technicians. Secondly, it provides a highly detailed visual, auditory, and motion simulation of an actual flight experience rather than a static airplane. This provides better exposure to the fear-triggering factors, potentially inducing participant responses more similar to those elicited by real air travel. Finally, other measures like heart rate and blood pressure can be recorded during VR exposure therapy to provide therapists with more comprehensive clinical information.The current results show that number of flights and flight hours post-treatment significantly increased, reflecting treatment efficacy. These results are in line with other retrospective follow-up studies assessing the efficacy of other virtual reality-based FoF treatments . The resWhile previous studies evaluating the efficacy of FoF-VRET used air travel in the post-treatment period  as the sole (binary) outcome e.g., , the curG = 0.592) and a significant increase in flight activity at follow-up (G = 0.588), demonstrating the advantage of FoF-VRET treatment over control/traditional FoF treatments. However, their results also reveal the limitations of these trials due to poor study quality and small sample size. The authors suggest that reported effects may have been overestimated as a result of these issues. In contrast, our findings are based on a larger sample size and a more true-to-life  environment than those of the aforementioned studies.In a recent meta-analysis of 11 randomized controlled trials, Some of our results elucidate clinical aspects of FoF and its treatment. While most participants reported suffering specifically from FoF (acrophobia), a significant number of participants reported suffering from general anxiety. Furthermore, almost half (48%) of the individuals receiving FoF-VRET treatment reported that they did not engage in any other treatments at least 1 year prior to treatment, suggesting that half of those suffering from FoF are untreated and may avoid air travel.The current study is limited in several important ways. Firstly, to maximize sample size, we did not collect data at a fixed length of time from treatment . Consequently, some adjustments to the data were required . Secondly, the attrition rate was relatively high (51.8%), which may have affected the results. Although this level of attrition was higher than in other retrospective follow-up studies 13% in , a higheFinally, due to the nature of the study, only participants who actively sought the FoF-VRET were included. This sample of participants may have been biased as they likely had greater motivation to treat their FoF and fewer psychological barriers relative to others with fear of flying. Future studies may attempt to address this limitation by evaluating a broader sample.As FoF severity was not assessed during treatment, future studies should examine the relation between FoF severity and FoF-VRET treatment outcome.Current results are indicative of FoF-VRET treatment efficacy. Air travel is an integral part of modern life in the industrialized world, and its prevalence is expected to grow as airfares continue to decrease and global economics entails more business travel . We can Unidentified data supporting the conclusions of this article will be made available by the authors upon reasonable request.The studies involving human participants were reviewed and approved by the Sheba Medical Center Local IRB Committee. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.AG performed some of the phone surveys, analyzed the data, and drafted the manuscript. GD drafted the manuscript. YH performed some of the phone surveys and analyzed the data. SN designed the study. MP designed the study, analyzed the data, and drafted the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Further, the authors declare no personal conflicts of interest. AG and MP are employees of Sheba Medical Center, and GD and YH were employed by Sheba Medical Center when conducting the research. Sheba Medical Center developed and offered the VR-based fear of flight treatment described here for clinical care of its patients.


Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI.N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units).We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort , OR for child BMI-GRS: 1.56 , and OR for child obesity-GRS 1.46 ]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85–0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS.GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children. Genetic determinants are known to affect childhood adiposity, measured by body mass index (BMI) as a quantitative trait or its upper extreme, overweight or obesity –4. NumerFTO locus and BMI varies by age [There is a large overlap between adiposity-associated genetic variants identified in adults and children. Among the 27 child BMI SNP, there are 22 SNPs that are either the same as or in high LD with SNPs identified for adult BMI . Similars by age , 16.Maternal adiposity is a major risk predictor of childhood adiposity . GeneticWe now performed an analysis in the same DNBC population of mother-child pairs but leveraged on child-specific GRSs in children, comprised of genetic variants identified in GWASs of children, as a more specific variable for childhood adiposity than the GRS for adult BMI used in the previous study. We utilized a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS. Our aim was to test whether the child GRSs for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, and whether the associations are modified by maternal BMI.N = 499); (2) children with overweight at 7 years of age and their mothers ; (3) mothers with overweight and their children . This selection provides the opportunity to perform a general survey of the study population (within the REF group), and apply a case-cohort design (including the CH-OW and REF groups) and an exposure-based cohort design (including the MO-OW and REF groups) for childhood overweight  . BMI of N = 26 independent SNPs) included 24 SNPs from the most recent EGG consortium GWAS meta-analysis of childhood BMI in 2020 [RAB27B) and rs3829849 (near LMX1B) that were identified in the 2016 EGG consortium meta-analysis of childhood BMI [N = 17 independent SNPs) included 16 SNPs from the most recent EGG consortium GWAS meta-analysis of childhood obesity [OLFM4) that was identified in the 2012 EGG consortium meta-analysis of childhood obesity [r2 > 0.1), the ones derived from the largest sample sizes were included in the child adiposity-GRS. We standardized all GRSs into z-scores based on mean and SD of the respective GRS in the REF group.We previously described detailed information on genotyping procedures using Illumina platforms, calling of genotypes, and genotype quality control of the children, encompassing the exclusion of ethnic outliers, of the three groups  . Genotyp in 2020 , plus rs near LMXB that we obesity , plus rs obesity  or odds  obesity  reportedz-score as the outcome (linear regression). In the case-cohort analyses, we combined the CH-OW and REF groups to estimate the ORs for being selected into the CH-OW group (presented with 95% CI). In the exposure-based cohort design analysis, we combined the MO-OW and REF groups, to estimate the ORs for childhood overweight at 7 years as based on the IOTF criteria. In sensitivity analysis, we tested whether the larger (combined) child adiposity-GRS would strengthen the results of the smaller child BMI-GRS and child obesity-GRS. We did not adjust any of the models for age or sex of the child because, by construction, child BMI z-score is age- and sex-specific. An overview of the participant flowchart and the selection of children and mothers into the REF, CH-OW, and MO-OW are shown in Fig. All analyses were conducted using R, version 3.6.3. We chose childhood overweight as outcome since the prevalence of childhood obesity at 7 years is so low in two of the three groups that the statistical power would be very limited and hence provide much more uncertain results than those based on childhood overweight  and nonsignificant in all three groups of mother-child dyads , child BMI-GRS: 0.17 SD , child obesity-GRS: 0.22 SD , Table In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for the children being in the CH-OW group [OR for maternal BMI: 2.01  OR for child BMI-GRS: 1.56 , OR for child obesity-GRS 1.46  per SD unit, Table p for interaction for child BMI-GRS × maternal BMI = 0.016, p for interaction for child obesity-GRS × maternal BMI = 0.005). The interaction effects were modest, suggesting 0.85–0.87-fold attenuation in the association between child GRSs or maternal BMI with ORs of overweight per SD unit increase in maternal BMI or child GRSs, respectively , OR for child BMI-GRS: 1.37 , OR for child obesity-GRS 1.41  per SD unit, Table z-score/odds of child overweight. However, the effect sizes seen for the child adiposity-GRS were generally slightly weaker  of the included genetic variants as reported by the respective discovery GWAS, which was not immediately possible when combining them. Another strength of our study is the sampling design based on mother-child pairs with extreme BMI conditions within the large DNBC: mothers with overweight and their children, children with overweight and their mothers and a reference group of randomly selected mothers and their children. The statistical power of the applied case-cohort and exposure-based cohort design is demonstrated by the precision of the estimates. Furthermore, chosing BMI and overweight at around age 7 years as outcome avoids challenges implicit in the childhood pattern of growth in BMI, which does not follow a linear trajectory from birth until adolescence. Thus, childhood BMI is characterized by a rapid increase from birth to around 9 months reaching adiposity peak, a decline from 9 months to 5 or 6 years of age, followed by a steady increase until adolescence during a phase called the “adiposity rebound”, and finally decelerated growth towards adulthood [z-scores in our study, we avoided the adiposity decline period before adiposity rebound as well as the specific pubertal effects on adiposity, where there are considerable differences in the growth curves between boys and girls.A major strength of the present study is the application of the child GRSs based on common genetic variants identified in large GWAS analysis that were specifically conducted in children, showing strong associations with child BMI and overweight in our study. We also defined a child adiposity-GRS by combining genetic variants identified for child BMI and child obesity to test whether this larger GRS would have the ability to strengthen the results of the smaller child BMI-GRS and child obesity-GRS. The overall weaker effect sizes seen for the child adiposity-GRS are likely due to the fact that, in contrast to both the child BMI-GRS and the child obesity-GRS, this GRS was not weighted by the effect sizes (dulthood . By usinWe found an attenuation of the effect of the child GRSs on childhood adiposity with increasing maternal BMI in mothers with overweight, confirming our previous observation . The intRecently, a large GRS for childhood adiposity, including 295 genetic variants, was generated in UK Biobank, in which adult participants provided questionnaire-derived data about their relative body size at 10 years of age . Such quThe strength of the association of child GRSs with adiposity-related traits is too weak to be useful for clinical risk prediction of child overweight. Moreover, applying GRS approaches to overweight risk assessment offers little in the absence of more detailed information, both about the specific effects of the predisposing SNPs, whether or not captured by the GRS, and about the lifestyle and environment of the individual mother-child dyads . HoweverIn conclusion, we confirm that child GRSs for adiposity-related traits and maternal BMI are both associated with childhood adiposity. We did not find evidence that maternal BMI within the normal range influences or modifies the effect of child GRSs for adiposity-related traits on childhood adiposity, suggesting that GRSs for childhood adiposity operate independently of the BMI of their mothers. However, in children of mothers with overweight the effect of child GRSs on childhood overweight was attenuated.Supplemental Appendix