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We examined partner-seeking and sexual behaviors among a representative sample of U.S. adults (N = 1,161) during the first year of the COVID-19 pandemic. Approximately 10% of survey respondents sought a new partner, with age and sexual identity being associated with partner seeking behavior. Approximately 7% of respondents had sex with a new partner, which marks a decrease as compared to a pre-pandemic estimate from 2015 - 2016 in which 16% of U.S. adults reported having sex with a new partner during the past year. Among respondents who had in-person sex with a new partner during the first year of the pandemic, public health guidelines for in-person sexual activity were infrequently followed.

For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35–50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a ‘watch and wait’ strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a ‘watch and wait’ strategy for ESCC treated with ChemoRT.

Behavioral responses such as social distancing are important in the fight to contain COVID‐19 transmission, yet motivating such responses is an overwhelming, resource‐intensive task. Using multi‐wave data from 23,735 US adults collected in May/September 2020, and January 2021, this study examines how financial preparedness in the form of savings influences the relationship predicted by the Health Belief Model between the degree of concern for COVID‐19 and engagement in social distancing. Findings indicate that general concern for COVID‐19 is related to the decision to engage in social distancing for individuals who have less saved. Curiously, higher levels of financial preparedness are associated with a lower likelihood of social distancing at least among people who had been laid off during the pandemic. The findings suggest a tradeoff between protecting one's standard of living and their health. Government and public health agencies should consider financial preparedness in the design of public health communications. [ABSTRACT FROM AUTHOR] Copyright of Journal of Consumer Affairs is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

High-intensity interval training (HIIT) promotes positive cardiometabolic and body composition changes. Essential amino acids (EAA) may support changes associated with HIIT, but evaluation of potential synergistic effects is lacking. The purpose of this study was to compare independent and combined effects of HIIT and EAA on total body composition and metabolism in men and women considered overweight/obese; an exploratory aim was to evaluate the modulatory effects of sex. Sixty-six healthy adults (50% female; Age: 36.7 ± 6.0 years; BMI: 32.0 ± 4.2 kg/m2) completed 8 weeks of: (1) HIIT, 2 days/weeks; (2) EAA supplementation, 3.6 g twice daily; (3) HIIT + EAA; or (4) control. Body composition, resting metabolic rate (RMR), substrate metabolism (respiratory exchange ratio; RER), and cardiorespiratory fitness were measured at baseline, 4 weeks, and 8 weeks; cardiometabolic blood markers were measured at baseline and 8 weeks. Differences between groups were assessed by linear mixed models covaried for baseline values, followed by 95% confidence intervals (CI) on adjusted mean change scores. There were no significant changes in body composition (p > 0.05) for any group. Changes in RER, but not RMR, occurred with HIIT (mean change; [95% CI]: − 0.04; [− 0.07, − 0.02]) and EAA (− 0.03; [− 0.06, − 0.01]) after 8 weeks. Cardiorespiratory fitness increased following 8 weeks of HIIT (+ 5.1 ml/kg/min [3.3,6.8]) and HIIT + EAA (+ 4.1 ml/kg/min [1.0,6.4]). Changes with HIIT + EAA were not significantly different from HIIT. There were no changes in cardiometabolic markers (p > 0.05) and no sex interaction (p > 0.05). HIIT is efficacious for promoting positive changes in cardiorespiratory fitness and resting substrate metabolism in adults considered overweight/obese. Addition of EAA did not significantly enhance HIIT-induced adaptations. ClinicalTrials.gov ID#NCT04080102.

Introduction: With the unprecedented expansion of women's roles in the U.S. military during recent (post-9/11) conflicts in Iraq and Afghanistan, the number of women seeking healthcare through the Veterans Health Administration (VHA) has increased substantially. Women Veterans often present as medically complex due to multiple medical, mental health, and psychosocial comorbidities, and consequently may be underserved. Thus, we conducted the nationwide Women Veterans Cohort Study (WVCS) to examine post-9/11 Veterans' unique healthcare needs and to identify potential disparities in health outcomes and care. Methods: We present baseline data from a comprehensive questionnaire battery that was administered from 2016 to 2019 to a national sample of post-9/11 men and women Veterans who enrolled in Veterans Affairs care (WVCS2). Data were analyzed for descriptives and to compare characteristics by gender, including demographics; health risk factors and symptoms of cardiovascular disease, chronic pain, and mental health; healthcare utilization, access, and insurance. Results: WVCS2 included 1,141 Veterans (51% women). Women were younger, more diverse, and with higher educational attainment than men. Women also endorsed lower traditional cardiovascular risk factors and comorbidities (e.g., weight, hypertension) and greater nontraditional cardiovascular risk factors (e.g., trauma, psychological symptoms). More women reported single-site pain (e.g., neck, stomach, pelvic) and multisite pain, but did not differ from men in posttraumatic stress disorder (PTSD) symptoms or treatment for PTSD. Women seek care at VHA medical centers more frequently, often combined with outside health services, but do not significantly differ from men in their insurance coverage. Conclusion: Overall, this investigation indicates substantial variation in risk factors, health outcomes, and healthcare utilization among post-9/11 men and women Veterans. Further research is needed to determine best practices for managing women Veterans in the VHA healthcare system.

Preventing unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, among adolescents is a public health priority. This report presents prevalence estimates for condom and contraceptive use among sexually active U.S. high school students from the 2019 Youth Risk Behavior Survey. Behaviors examined included any condom use, primary contraceptive method use, and condom use with a more effective contraceptive method, all reported at last sexual intercourse. Analyses were limited to sexually active students (i.e., those who had sexual intercourse with one or more persons during the 3 months before the survey). Except for any condom use, students reporting only same-sex sexual contact were excluded from analyses. Weighted prevalence estimates were calculated, and bivariate differences in prevalence were examined by demographic characteristics (sex, race/ethnicity, and grade) and other sexual risk behaviors (age of sexual initiation, previous 3-month and lifetime number of sex partners, and substance use before last sexual intercourse). Nationwide, 27.4% of high school students reported being sexually active (n = 3,226). Among sexually active students who reported having had sexual contact with someone of the opposite sex (n = 2,698), most students (89.7%) had used a condom or a primary contraceptive method at last sexual intercourse. Prevalence of any condom use at last sexual intercourse was 54.3%, and condoms were the most prevalent primary contraceptive method (43.9% versus 23.3% for birth control pills; 4.8% for intrauterine device [IUD] or implant; and 3.3% for shot, patch, or ring). Approximately 9% had used condoms with an IUD, implant, shot, patch, ring, or birth control pills. Using no pregnancy prevention method was more common among non-Hispanic black (23.2%) and Hispanic (12.8%) students compared with non-Hispanic white students (6.8%); compared with Hispanic students, using no pregnancy prevention method was more common among non-Hispanic black students. Prevalence of condom use was consistently lower among students with other sexual risk behaviors. Results underscore the need for public health professionals to provide quality sexual and reproductive health education and clinical services for preventing unintended pregnancy and STDs/HIV and decreasing disparities among sexually active youths.

BACKGROUND: Recent increases in high-risk substance use (HRSU; i.e., injection drug use, heroin, methamphetamine, crack/cocaine) have coincided with rising primary and secondary (P&S) syphilis rates. To further understand these trends, we examined sexual risk behaviors among women, men who have sex with women only (MSW), and men who have sex with men (MSM) who were diagnosed with P&S syphilis in 2018 and reported HRSU. METHODS: Data on HRSU and sexual risk behaviors among persons with P&S syphilis were drawn from syphilis case reports in 2018 from the National Notifiable Diseases Surveillance System. Persons with P&S syphilis were asked about sexual risk behaviors in the past 12 months including exchange sex for drugs/money, sex while intoxicated and/or high on drugs, sex with a person who injects drugs (PWID), sex with an anonymous partner, and number of sex partners. We describe percentages and adjusted prevalence ratios (aPRs) for women, MSW, and MSM reporting these behaviors by age, race/Hispanic ethnicity, type of drug used, and incarceration history (both in the past 12 months). RESULTS: Among 19,634 persons diagnosed with P&S syphilis in 2018 with information on HRSU, 29.3% of women, 22.7% of MSW, and 12.4% of MSM reported HRSU. Among those reporting HRSU, percentages reporting exchange sex ranged from 17% to 35% (highest for women), whereas reports of anonymous sex ranged from 44% to 71% (highest for MSM). In this population, sexual risk behaviors were more commonly reported among those with a recent incarceration history than those without such history. Among those reporting injection drug use or heroin use, percentages reporting sex with a PWID ranged from 51% to 77%. In adjusted models, HRSU was significantly associated with one or more sexual risk behaviors for women (aPR, 2.63 [95% confidence interval {CI}, 2.39–2.90]; MSW: aPR, 1.38 [95% CI, 1.31–1.46]; and MSM: aPR, 1.30 [95% CI, 1.26–1.34]). CONCLUSIONS: Collaborative partnerships across the US public health system could help address barriers to timely clinical care among persons diagnosed with P&S syphilis who report HRSU.

Cabre, HE, Greenwalt, CE, Gould, LM, Hirsch, KR, Blue, MNM, and Smith-Ryan, AE. Exploring the "Athlete's Paradox": Division I cross-country runners demonstrate similar muscle characteristics to recreationally trained young adults. J Strength Cond Res XX(X): 000-000, 2021-Endurance training can influence body composition and muscle characteristics. Endurance athletes have demonstrated elevated intramuscular fat (IMF), yet individuals with greater body fat also demonstrate elevated IMF. The purpose of this study was to examine differences in muscle characteristics (echo intensity [EI] and muscle cross-sectional area [mCSA]) and body composition between Division I collegiate athletes and college-age adults matched for percent fat (%fat). Thirty cross-country athletes (XC) and 30 normal-weight (NW) recreationally active college students (male athletes: n = 30; female athletes: n = 30; mean ± SD: age: 19.2 ± 1.1 years; body mass: 61.7 ± 8.7 kg; %fat: 18.0 ± 5.2%) underwent a panoramic ultrasound scan of the vastus lateralis to evaluate EI and mCSA. A full-body dual-energy x-ray absorptiometry scan was used to assess fat mass (FM), lean mass (LM), and %fat. Independent t-tests were used to evaluate mCSA, EI, and body composition. Significance level was set at ≤ 0.05. There were no significant differences between the XC and NW cohorts in mCSA (mean difference [MD; XC - NW], -1.30 ± -0.40 cm3; p = 0.340) or EI (MD: 3.97 ± 2.66 a.u.; p = 0.478). Body composition was not different between the groups: FM (MD: -0.14 ± -0.54 kg; p = 0.848), LM (-3.07 ± 1.25 kg; p = 0.268), or bone mineral content (-0.21 ± 0.03 kg; p = 0.120). There were also no significant differences for any outcome variables when stratified by male athletes (p = 0.097-0.468) or female athletes (p = 0.055-0.700). These results suggest that XC athletes may have similar muscle characteristics to NW individuals when matched for %fat. Understanding and tracking muscle characteristics in XC athletes may be important for performance, injury prevention, and the transition to retirement.

Background The potential long-term effects of childhood fluoxetine therapy on brain serotonin systems were studied using a nonhuman primate model, the rhesus monkey. Methods Juvenile male rhesus (1–4 years of age, corresponding to 4–11 years of age in children) were treated orally with fluoxetine (2 mg/kg) or vehicle daily for 2 years and removed from treatment during the third year. Each treatment group was assigned an equal number of subjects with low and high transcription polymorphisms of MAOA. One year after discontinuation of treatment, positron emission tomography scans were conducted (n = 8 treated monkeys, n = 8 control monkeys) using [11C]DASB to quantify serotonin transporter in 16 cortical and subcortical regions. Results Fluoxetine-treated monkeys with MAOA low transcription polymorphism had significantly lower [11C]DASB binding potentials than control monkeys. This finding was seen throughout the brain but was strongest in prefrontal and cingulate cortices. The MAOA × fluoxetine interaction was enhanced by binding potentials that were nonsignificantly higher in monkeys with high transcription polymorphism. Conclusions Juvenile fluoxetine treatment has residual posttreatment effects on brain serotonin transporter that depend on MAOA genotype. MAOA genotype may be important to consider when treating children with fluoxetine.

Background and Purpose— In older populations, transient ischemic attack (TIA) and ischemic stroke have been linked to psychological factors, including posttraumatic stress disorder (PTSD). Whether PTSD also increases risk for early incident stroke in young adults is unknown. Methods— We prospectively assessed the incidence of TIA and ischemic stroke in a cohort of 987 855 young and middle-aged Veterans (mean age of 30.29±9.19 years; 87.8% men, 64.4% white) who first accessed care through the Veterans Health Administration from October 2001 to November 2014 and were free of TIA and ischemic stroke at baseline. For each outcome, time-varying multivariate Cox models were constructed to examine the effect of PTSD on incident stroke. We also assessed for effect modification by sex. Additional sensitivity analyses controlled for healthcare utilization. Results— Over a 13-year period, TIA and ischemic stroke were diagnosed in 766 and 1877 patients, respectively. PTSD was diagnosed in 28.6% of the sample during follow-up. In unadjusted analyses, PTSD was significantly associated with new-onset TIA (hazard ratio [HR], 2.02; 95% CI, 1.62–2.52) and ischemic stroke (HR, 1.62; 95% CI, 1.47–1.79). In fully adjusted models, the association between PTSD and incident TIA (HR, 1.61; 95% CI, 1.27–2.04) and ischemic stroke (HR, 1.36; 95% CI, 1.22–1.52) remained significant. The effect of PTSD on ischemic stroke risk was stronger in men than in women (HR, 0.63; 95% CI, 0.47–0.86; P =0.003), but no effect of sex was found for TIA. Conclusions— PTSD is associated with a significant increase in risk of early incident TIA and ischemic stroke independent of established stroke risk factors, coexisting psychiatric disorders, and healthcare utilization. Sex moderated the relationship for adults with ischemic stroke but not TIA. These findings suggest that psychological factors, including PTSD, may be important targets for future age-specific prevention strategies for young adults.

BACKGROUND Although adhesive small-bowel obstruction (ASBO) is frequently managed nonoperatively, little is known regarding outcomes on readmission following this approach. Using a large population-based dataset, we evaluated risk factors for operative intervention and mortality at readmission in patients with ASBO who were initially managed nonoperatively. METHODS The ASBO patients were identified in the California Office of Statewide Health Planning and Development 2007 to 2014 patient discharge database. Patients who were managed operatively at index admission or had an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for nonadhesive obstructive small bowel disease were excluded. Associations between risk factors and both operative intervention and death following readmission were evaluated using survival analysis. RESULTS Among 15,963 ASBO patients, 3,103 (19.4%) had at least one readmission. The 1,069 (34.5%) who received an operation during their first readmission presented sooner (175 days vs. 316 days, p < 0.001) and were more likely to die during that readmission (5.2% vs. 0.7%, p < 0.001). Operative management at first readmission was associated with younger age, fewer comorbidities, and shorter times to readmission. Patients operatively managed at first readmission had longer times to second readmission compared with nonoperative patients. Stratified analyses using nonoperative patients as the reference over the study period revealed that patients who underwent lysis of adhesions and bowel resection were 5.04 times (95% confidence interval [CI], 2.82-9.00) as likely to die while those who underwent lysis only were 2.09 times (95% CI, 1.14-3.85) as likely to die. Patients with bowel resection only were at an increased risk for subsequent interventions beyond the first readmission (hazard ratio, 1.79; 95% CI, 1.11-2.87). CONCLUSION In a large cohort readmitted for ASBO and initially managed nonoperatively, subsequent operative intervention conferred a greater risk of death and a longer time to readmission among survivors. Prospective research is needed to further delineate outcomes associated with initial nonoperative management of ASBO. LEVEL OF EVIDENCE Prognostic and epidemiological, level III.

Outcomes following damage control laparotomy for trauma have been studied in detail. However, outcomes following a single operation, or "single-look trauma laparotomy" (SLTL), have not. We evaluated the association between SLTL and both short-term and long-term outcomes in a large population-based data set.The California Office of Statewide Health Planning and Development patient discharge database was evaluated for calendar years 2007 through 2014. Injured patients with SLTL during their index admission were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. Diagnosis and procedure codes were used to identify specific abdominal organ injuries, surgical interventions, and perioperative complications. Subsequent acute care admissions were examined for postoperative complications and related surgical interventions. Clinical characteristics, injuries, surgical interventions, and outcomes were analyzed by mechanism of injury.There were 2113 patients with SLTL during their index admission; 712 (33.7%) had at least one readmission to an acute care facility. Median time to first readmission was 110 days. Penetrating mechanism was more common than blunt (60.6% vs. 39.4%). Compared to patients with penetrating injury, blunt-injured patients had a significantly higher median Injury Severity Score (9 vs. 18, p0.0001) and a significantly higher mortality rate during the index admission (4.1% vs. 27.0%, p0.0001). More than 30% of SLTL patients requiring readmission had a surgery-related complication. The most common primary reasons for readmission were bowel obstruction (17.7%), incisional hernia (11.8%), and infection (9.1%). There was no significant association between mechanism of injury and development of surgery-related complications requiring readmission.Patients with SLTL had postinjury morbidity and mortality, and more than 30% required readmission. Complication rates for SLTL were comparable to those reported for emergency general surgery procedures. Patients should be educated on signs and symptoms of the most common complications before discharge following SLTL. Further investigation should focus on the factors associated with the development of these complications.Prognostic and epidemiologic study, level III.

BackgroundDamage control laparotomy (DCL) is a life-saving procedure in patients with abdominal hemorrhage. After DCL, patients are sometimes left with an open abdomen (OA) so they may undergo multiple exploratory laparotomies (EXLAP), or re-explorations. Patients with OA are at increased risk of infectious complications (ICs). The association between number of re-explorations after DCL and the number of ICs is not clear. We hypothesized that each additional re-exploration increases the risk of developing IC.MethodsThis 6-year retrospective cohort study included patients aged ≥16 years from the NTDB who had DCL defined as EXLAP within 2 hours of arrival (ICD-9: 54.11, 54.12, 54.19) with at least one re-exploration. The primary outcome was IC (ie, superficial surgical site infection (SSI), organ space SSI, deep SSI, sepsis, pneumonia, or catheter-related bloodstream infection), examined dichotomously (present/absent) and ordinally as the number of ICs. Multivariate Poisson regression was used to assess the association between number of re-explorations and number of ICs. Significance was assigned at pResultsThere were 7431 patients who underwent DCL; 2509 (34%) patients developed at least one IC. The rate of IC was lowest in patients who were closed during the first re-exploration (27%) and significantly increased with each re-exploration to 59% in patients who had five or more re-explorations (Cochran-Armitage trend pDiscussionFor patients requiring DCL, each re-exploration of the abdomen is associated with increased rate of ICs.Level of evidenceIII, retrospective epidemiological study.

The purpose of this study was to compare the independent and combined effects of high‐intensity interval training (HIIT) and essential amino acids (EAA) on lean mass, muscle characteristics of the quadriceps, and 24‐hr whole‐body protein turnover (WBPT) in overweight and obese adults. An exploratory aim was to evaluate potential modulatory effects of sex. Sixty‐six adults (50% female; Age: 36.7 ± 6.0 yrs; %BF: 36.0 ± 7.8%) were assigned to 8 wks of: (a) HIIT, 2 days/wk; (b) EAA supplementation, 3.6 g twice daily; (c) HIIT + EAA; or (d) control. At baseline, 4 wks, and 8 wks, total body, thigh LM and muscle characteristics were measured via dual‐energy x‐ray absorptiometry and B‐mode ultrasound, respectively. In a subsample, changes in WBPT was measured using [N15]alanine. Differences between groups were assessed using linear mixed models adjusted for baseline values, followed by 95% confidence intervals on adjusted mean change scores (Δ). HIIT and HIIT + EAA improved thigh LM (Δ: +0.17 ± 0.05 kg [0.08, 0.27]; +0.22 ± 0.05 kg [0.12,0.31]) and vastus lateralis cross‐sectional area (Δ: +2.73 ± 0.52 cm2 [1.69,3.77]; +2.64 ± 0.53 cm2 [1.58,3.70]), volume (Δ: +54.50 ± 11.69 cm3 [31.07, 77.92]; +62.39 ± 12.05 cm3 [38.26, 86.52]), and quality (Δ: −5.46 ± 2.68a.u. [−10.84, −0.09]; −7.97 ± 2.76a.u.[−13.49, −2.45]). Protein synthesis, breakdown, and flux were greater with HIIT + EAA and EAA compared to HIIT (p, In overweight and obese adults, eight weeks of high‐intensity interval training, with or without essential amino acid supplementation (EAA), improved thigh lean mass size and quality; EAA may enhance muscular adaptation via increases in protein turnover, supporting greater improvements in muscular size and quality.

S100-negative CD1a-positive cutaneous histiocytosis is an exceedingly rare histiocytosis that is defined histopathologically by a dense dermal infiltrate of ovoid mononuclear cells with grooved nuclei and ample cytoplasm with variable nuclear atypia and mitoses that are immunohistochemically positive for CD1a and negative for S100 and CD207 (langerin). The histogenesis of S100-negative CD1a-positive histiocytosis is unclear, and its precursor cell has yet to be characterized. Although all cases thus far have been described as benign and occasionally self-resolving, the clinical course and outcome of this disease are not fully understood. This case expands the spectrum of disease associated with S100-negative CD1a-positive histiocytosis given its malignant course.

Background Pain and heart failure are highly comorbid. Objectives The purpose of this study was to examine differences in pain intensity and pain medication prescriptions among Veterans with comorbid heart failure and pain and those with pain alone. Methods The Musculoskeletal Disorder (MSD) cohort includes 5,237,763 Veteran diagnosed with a musculoskeletal disorder between 2000 and 2013. Veterans with comorbid heart failure and back pain (heart failure+, n = 3,950, Mage = 70.5 ± 12) were compared to those with back pain alone (heart failure-, n = 165,290, Mage = 52.1 ± 17.5). Results In multivariate adjusted models, heart failure+ was associated with a higher likelihood of moderate/severe pain (OR = 1.12; 95% CI 1.04–1.21), a higher likelihood of opioids (OR = 1.63; CI = 1.52–1.75) and/or gabapentin prescriptions (OR = 1.18; CI = 1.02–1.36), but a lower likelihood of NSAID prescriptions (OR = 0.57; CI = 0.50–0.66). Conclusions Comorbid cardiovascular and pain conditions present a challenge in clinical management that warrants further study.

Skilled nursing facilities (SNFs) are focal points of the coronavirus disease 2019 (COVID-19) pandemic, and asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19, among SNF residents and health care personnel have been described (1-3). Repeated point prevalence surveys (serial testing of all residents and health care personnel at a health care facility irrespective of symptoms) have been used to identify asymptomatic infections and have reduced SARS-CoV-2 transmission during SNF outbreaks (1,3). During March 2020, the Detroit Health Department and area hospitals detected a sharp increase in COVID-19 diagnoses, hospitalizations, and associated deaths among SNF residents. The Detroit Health Department collaborated with local government, academic, and health care system partners and a CDC field team to rapidly expand SARS-CoV-2 testing and implement infection prevention and control (IPC) activities in all Detroit-area SNFs. During March 7-May 8, among 2,773 residents of 26 Detroit SNFs, 1,207 laboratory-confirmed cases of COVID-19 were identified during three periods: before (March 7-April 7) and after two point prevalence surveys (April 8-25 and April 30-May 8): the overall attack rate was 44%. Within 21 days of receiving their first positive test results, 446 (37%) of 1,207 COVID-19 patients were hospitalized, and 287 (24%) died. Among facilities participating in both surveys (n = 12), the percentage of positive test results declined from 35% to 18%. Repeated point prevalence surveys in SNFs identified asymptomatic COVID-19 cases, informed cohorting and IPC practices aimed at reducing transmission, and guided prioritization of health department resources for facilities experiencing high levels of SARS-CoV-2 transmission. With the increased availability of SARS-CoV-2 testing, repeated point prevalence surveys and enhanced and expanded IPC support should be standard tools for interrupting and preventing COVID-19 outbreaks in SNFs.

Apolipoprotein E (APOE) e4 genotype is associated with increased risk of dementia in Parkinson's disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies. APOE e4 exacerbates brain Aβ pathology, as well as tau pathology, but it is not clear whether APOE genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on Apoe knockout (A53T/EKO) or human APOE knockin backgrounds (A53T/E2, E3, and E4). At 12 months of age, A53T/E4 mice accumulated higher amounts of brainstem detergent-insoluble phosphorylated αSyn compared to A53T/EKO and A53T/E3; detergent-insoluble αSyn in A53T/E2 mice was undetectable. By immunohistochemistry, A53T/E4 mice displayed a higher burden of phosphorylated αSyn and reactive gliosis compared to A53T/E2 mice. A53T/E2 mice exhibited increased survival and improved motor performance compared to other APOE genotypes. In a complementary model of αSyn spreading, striatal injection of αSyn preformed fibrils induced greater accumulation of αSyn pathology in the substantia nigra of A53T/E4 mice compared to A53T/E2 and A53T/EKO mice. In two separate cohorts of human patients with PD, APOE e4/e4 individuals showed the fastest rate of cognitive decline over time. Our results demonstrate that APOE genotype directly regulates αSyn pathology independent of its established effects on Aβ and tau, corroborate the finding that APOE e4 exacerbates pathology, and suggest that APOE e2 may protect against αSyn aggregation and neurodegeneration in synucleinopathies.

Orthopedic biomaterial-associated infections remain a large clinical challenge, particularly with open fractures and segmental bone loss. Invasion and colonization of bacteria within immune-privileged canalicular networks of the bone can lead to local, indolent infections that can persist for years without symptoms before eventual catastrophic hardware failure. Host immunity is essential for bacterial clearance and an appropriate healing response, and recent evidence has suggested an association between orthopedic trauma and systemic immune dysregulation and immunosuppression. However, the impact of a local infection on this systemic immune response and subsequent effects on the local response is poorly understood and has not been a major focus for addressing orthopedic injuries and infections. Therefore, this study utilized a model of orthopedic biomaterial-associated infection to investigate the effects of infection on the long-term immune response. Here, despite persistence of a local, indolent infection lacking outward symptoms, there was still evidence of long-term immune dysregulation with systemic increases in MDSCs and decreases in T cells compared to non-infected trauma. Further, the trauma only group exhibited a regulated and coordinated systemic cytokine response, which was not present in the infected trauma group. Locally, the infection group had attenuated macrophage infiltration in the local soft tissue compared to the non-infected group. Our results demonstrate widespread impacts of a localized orthopedic infection on the systemic and local immune responses. Characterization of the immune response to orthopedic biomaterial-associated infection may identify key targets for immunotherapies that could optimize both regenerative and antibiotic interventions, ultimately improving outcomes for these patients.

The efficacy of psychological and pharmacotherapy interventions for the treatment of depression in cardiac populations and secondarily, the effect of these treatments on cardiovascular outcomes, has been a major focus in the clinical trials literature. Research provides modest support for psychological interventions for improving depression severity and promoting depression remission in these patients, with support also evident for the use of pharmacotherapy interventions in these populations. Yet, the effects of these interventions on cardiovascular outcomes has at best been inconsistent. The clinical trial literature is limited by trials with small, homogenous samples, short follow-up periods, and low or unknown treatment fidelity. The complexity of depression as a clinical syndrome, along with questions concerning implementation should be included in the design of future clinical trials, whether targeting depression alone, or the medical consequences of depression for patients with cardiovascular disease.

Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients. The purpose of this study was to determine the time to stroke in patients with a BCVI-related stroke. We hypothesized that the majority of patients suffer stroke between 24 hours and 72 hours after injury.Patients with a BCVI-related stroke from January 2007 to January 2017 from 37 trauma centers were reviewed.During the 10-year study, 492 patients had a BCVI-related stroke; the majority were men (61%), with a median age of 39 years and ISS of 29. Stroke was present at admission in 182 patients (37%) and occurred during an Interventional Radiology procedure in six patients. In the remaining 304 patients, stroke was identified a median of 48 hours after admission: 53 hours in the 144 patients identified by neurologic symptoms and 42 hours in the 160 patients without a neurologic examination and an incidental stroke identified on imaging. Of those patients with neurologic symptoms, 88 (61%) had a stroke within 72 hours, whereas 56 had a stroke after 72 hours; there was a sequential decline in stroke occurrence over the first week. Of the 304 patients who had a stroke after admission, 64 patients (22%) were being treated with antithrombotics when the stroke occurred.The majority of patients suffer BCVI-related stroke in the first 72 hours after injury. Time to stroke can help inform clinicians about initiation of treatment in the multiply injured patient.Prognostic/Epidemiologic, level III.

Objective The objective is to provide guidance for pregnant women, and obstetric care and exercise professionals, on prenatal physical activity. Outcomes The outcomes evaluated were maternal, fetal, or neonatal morbidity or fetal mortality during and following pregnancy. Evidence Literature was retrieved through searches of Medline, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus and Web of Science Core Collection, CINAHL Plus with Full-text, Child Development & Adolescent Studies, ERIC, Sport Discus, ClinicalTrials.gov, and the Trip Database from database inception up to January 6, 2017. Primary studies of any design were eligible, except case studies. Results were limited to English, Spanish, or French language materials. Articles related to maternal physical activity during pregnancy reporting on maternal, fetal, or neonatal morbidity or fetal mortality were eligible for inclusion. The quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Values The Guidelines Consensus Panel solicited feedback from end-users (obstetric care providers, exercise professionals, researchers, policy organizations, and pregnant and postpartum women). The development of this guideline followed the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument. Benefits, harms, and costs The benefits of prenatal physical activity are moderate, and no harms were identified; therefore, the difference between desirable and undesirable consequences (net benefit) is expected to be moderate. The majority of stakeholders and end-users indicated that following these recommendations would be feasible, acceptable, and equitable. Following these recommendations is likely to require minimal resources from both individual and health systems perspectives. Preamble This guideline provide evidence-based recommendations regarding physical activity throughout pregnancy in the promotion of maternal, fetal, and neonatal health. In the absence of contraindications (see later for a detailed list), following this guideline is associated with: (1) fewer newborn complications (i.e., large for gestational age); and (2) maternal health benefits (i.e., decreased risk of preeclampsia, gestational hypertension, gestational diabetes, Caesarean section, instrumental delivery, urinary incontinence, excessive gestational weight gain, and depression; improved blood glucose; decreased total gestational weight gain; and decreased severity of depressive symptoms and lumbopelvic pain). Physical activity is not associated with miscarriage, stillbirth, neonatal death, preterm birth, preterm/prelabour rupture of membranes, neonatal hypoglycemia, low birth weight, birth defects, induction of labour, or birth complications. In general, more physical activity (frequency, duration, and/or volume) is associated with greater benefits. However, evidence was not identified regarding the safety or additional benefit of exercising at levels significantly above the recommendations. Prenatal physical activity should be considered a front-line therapy for reducing the risk of pregnancy complications and enhancing maternal physical and mental health. For pregnant women not currently meeting this guideline, a progressive adjustment toward them is recommended. Previously active women may continue physical activity throughout pregnancy. Women may need to modify physical activity as pregnancy progresses. There may be periods when following the guideline is not possible due to fatigue and/or discomforts of pregnancy; women are encouraged to do what they can and to return to following the recommendations when they are able. This guideline were informed by an extensive systematic review of the literature, expert opinion, end-user consultation and considerations of feasibility, acceptability, costs, and equity. Recommendations The specific recommendations in this 2019 Canadian Guideline for Physical Activity Throughout Pregnancy are provided below with corresponding statements indicating the quality of the evidence informing the recommendations and the strength of the recommendations (explanations follow). Contraindications All pregnant women can participate in physical activity throughout pregnancy with the exception of those who have contraindications (listed below). Women with absolute contraindications may continue their usual activities of daily living but should not participate in more strenuous activities. Women with relative contraindications should discuss the advantages and disadvantages of moderate-to-vigorous intensity physical activity with their obstetric care provider prior to participation. Absolute contraindications to exercise are the following: Relative contraindications to exercise are the following: STRENGTH OF THE RECOMMENDATIONS: The GRADE system was utilized to grade the strength of the recommendations. Recommendations are rated as strong or weak based on the: (1) balance between benefits and harms; (2) overall quality of the evidence; (3) importance of outcomes (i.e., values and preferences of pregnant women); (4) use of resources (i.e., cost); (5) impact on health equity; (6) feasibility, and (7) acceptability. Strong recommendation: Most or all pregnant women will be best served by the recommended course of action. Weak recommendation: Not all pregnant women will be best served by the recommended course of action; there is a need to consider other factors such as the individual's circumstances, preferences, values, resources available, or setting. Consultation with an obstetric care provider may assist in decision-making. Quality of the evidence The quality of the evidence refers to the level of confidence in the evidence and ranges from very low to high. High quality: The Guideline Consensus Panel is very confident that the estimated effect of physical activity on the health outcome is close to the true effect. Moderate quality: The Guideline Consensus Panel is moderately confident in the estimated effect of physical activity on the health outcome; the estimate of the effect is likely to be close to the true effect, but there is a possibility that it is substantially different. Low quality: The Guideline Consensus Panel's confidence in the estimated effect of physical activity on the health outcome is limited; the estimate of the effect may be substantially different from the true effect. Very low quality: The Guideline Consensus Panel has very little confidence in the estimated effect of physical activity on the health outcome; the estimate of the effect is likely to be substantially different from the true effect. aThis was a weak recommendation because the quality of evidence was low, and the net benefit between women who were physically active and those who were not was small. bThis was a strong recommendation because, despite low quality evidence supporting physical activity during pregnancy for women categorized as overweight or obese, there was evidence from randomized controlled trials demonstrating an improvement in gestational weight gain and blood glucose. cModerate-intensity physical activity is intense enough to noticeably increase heart rate; a person can talk but not sing during activities of this intensity. Examples of moderate-intensity physical activity include brisk walking, water aerobics, stationary cycling (moderate effort), resistance training, carrying moderate loads, and household chores (e.g., gardening, washing windows). dThis was a weak recommendation because urinary incontinence was was not rated as a "critical" outcome and the evidence was low quality. eThis was a weak recommendation because: (1) the quality of evidence was very low; and (2) although harms were investigated there was limited available information to inform the balance of benefits and harms. This recommendation was primarily based on expert opinion.

In the last decade, an abundance of new research from Canada and internationally has provided substantial evidence for the efficacy of exercise in preventing pregnancy complications and improving long-term maternal and fetal outcomes. Indeed, guidelines for exercise during pregnancy are available from several countries. This includes the expert consensus-based 2003 Joint SOGC and Canadian Society for Exercise Physiology Clinical Practice Guidelines: Exercise in Pregnancy and the Postpartum Period. With the plethora of new scientific evidence, it was vital to re-examine the literature by using the rigorous process followed by previous Canadian health behaviour guidelines.The purpose of this document is to outline the process and outcomes for the re-development of the 2019 Canadian Guideline for Physical Activity Throughout Pregnancy, herein referred to as the Guidelines. The target users for these Guidelines are obstetric care providers, policymakers, and exercise professionals who provide guidance for pregnant women regarding prenatal physical activity.

ObjectiveTo examine the relationships between prenatal physical activity and prenatal and postnatal urinary incontinence (UI).DesignSystematic review with random effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [e.g., dietary; “exercise + co-intervention”]), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcome (prenatal or postnatal UI).Results24 studies (n=15 982 women) were included. ‘Low’ to ‘moderate’ quality evidence revealed prenatal pelvic floor muscle training (PFMT) with or without aerobic exercise decreased the odds of UI in pregnancy (15 randomised controlled trials (RCTs), n=2764 women; OR 0.50, 95% CI 0.37 to 0.68, I2=60%) and in the postpartum period (10 RCTs, n=1682 women; OR 0.63, 95% CI 0.51, 0.79, I2=0%). When we analysed the data by whether women were continent or incontinent prior to the intervention, exercise was beneficial at preventing the development of UI in women with continence, but not effective in treating UI in women with incontinence. There was ‘low’ quality evidence that prenatal exercise had a moderate effect in the reduction of UI symptom severity during (five RCTs, standard mean difference (SMD) −0.54, 95% CI −0.88 to –0.20, I2=64%) and following pregnancy (three RCTs, ‘moderate’ quality evidence; SMD −0.54, 95% CI −0.87 to –0.22, I2=24%).ConclusionPrenatal exercise including PFMT reduced the odds and symptom severity of prenatal and postnatal UI. This was the case for women who were continent before the intervention. Among women who were incontinent during pregnancy, exercise training was not therapeutic.

ObjectiveThe purpose of this review was to investigate the relationship between prenatal exercise, and low back (LBP), pelvic girdle (PGP) and lumbopelvic (LBPP) pain.DesignSystematic review with random effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were eligible (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (prevalence and symptom severity of LBP, PGP and LBPP).ResultsThe analyses included data from 32 studies (n=52 297 pregnant women). ‘Very low’ to ‘moderate’ quality evidence from 13 randomised controlled trials (RCTs) showed prenatal exercise did not reduce the odds of suffering from LBP, PGP and LBPP either in pregnancy or the postpartum period. However, ‘very low’ to ‘moderate’ quality evidence from 15 RCTs identified lower pain severity during pregnancy and the early postpartum period in women who exercised during pregnancy (standardised mean difference −1.03, 95% CI −1.58, –0.48) compared with those who did not exercise. These findings were supported by ‘very low’ quality evidence from other study designs.ConclusionCompared with not exercising, prenatal exercise decreased the severity of LBP, PGP or LBPP during and following pregnancy but did not decrease the odds of any of these conditions at any time point.

ObjectiveGestational weight gain (GWG) has been identified as a critical modifier of maternal and fetal health. This systematic review and meta-analysis aimed to examine the relationship between prenatal exercise, GWG and postpartum weight retention (PPWR).DesignSystematic review with random effects meta-analysis and meta-regression. Online databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs in English, Spanish or French were eligible (except case studies and reviews) if they contained information on the population (pregnant women without contraindication to exercise), intervention (frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume or type of exercise) and outcomes (GWG, excessive GWG (EGWG), inadequate GWG (IGWG) or PPWR).ResultsEighty-four unique studies (n=21 530) were included. ‘Low’ to ‘moderate’ quality evidence from randomised controlled trials (RCTs) showed that exercise-only interventions decreased total GWG (n=5819; −0.9 kg, 95% CI −1.23 to –0.57 kg, I2=52%) and PPWR (n=420; −0.92 kg, 95% CI −1.84 to 0.00 kg, I2=0%) and reduced the odds of EGWG (n=3519; OR 0.68, 95% CI 0.57 to 0.80, I2=12%) compared with no exercise. ‘High’ quality evidence indicated higher odds of IGWG with prenatal exercise-only (n=1628; OR 1.32, 95% CI 1.04 to 1.67, I2=0%) compared with no exercise.ConclusionsPrenatal exercise reduced the odds of EGWG and PPWR but increased the risk of IGWG. However, the latter result should be interpreted with caution because it was based on a limited number of studies (five RCTs).

ObjectiveTo investigate the relationships between exercise and incidence of congenital anomalies and hyperthermia.DesignSystematic review with random-effects meta-analysis .Data sourcesOnline databases were searched from inception up to 6 January 2017.Study eligibility criteriaStudies of all designs were eligible (except case studies and reviews) if they were published in English, Spanish or French, and contained information on population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [e.g., dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume or type of exercise) and outcome (maternal temperature and fetal anomalies).ResultsThis systematic review and meta-analysis included ‘very low’ quality evidence from 14 studies (n=78 735) reporting on prenatal exercise and the odds of congenital anomalies, and ‘very low’ to ‘low’ quality evidence from 15 studies (n=447) reporting on maternal temperature response to prenatal exercise. Prenatal exercise did not increase the odds of congenital anomalies (OR 1.23, 95% CI 0.77 to 1.95, I2=0%). A small but significant increase in maternal temperature was observed from pre-exercise to both during and immediately after exercise (during: 0.26°C, 95% CI 0.12 to 0.40, I2=70%; following: 0.24°C, 95% CI 0.17 to 0.31, I2=47%).Summary/ConclusionsThese data suggest that moderate-to-vigorous prenatal exercise does not induce hyperthermia or increase the odds of congenital anomalies. However, exercise responses were investigated in most studies after 12 weeks’ gestation when the risk of de novo congenital anomalies is negligible.

Research in affective science has shown that trait positive affect reduces the risk of developing disease and is protective against the progression of certain diseases. Research also suggests that trait positive affect predisposes individuals to more frequent experiences of positive emotional states. The undoing effect has been proposed as a potential mechanism explaining how positive emotions influence health outcomes. According to this hypothesis, the experience of state positive emotions or positive affect contributes to faster recovery from the body's physiological response to stress. This paper critically reviews literature concerning the undoing hypothesis. Several common methodological weaknesses were identified, including conceptual and design issues. Based on the reviewed studies two separate conclusions were drawn. First, there was insufficient evidence to conclude that the occurrence of positive emotional states speeds physiological recovery. Second, there was insufficient evidence to evaluate the undoing hypothesis as a potential mechanism through which state positive emotions affect health. Future research should focus on identifying the key parameters responsible for demonstrating the undoing effect when it is observed in order to understand how the experience of positive emotions may exert positive effects on health outcomes.

Severe musculoskeletal trauma is one of the most prevalent types of trauma in both combat-wounded and civilian patients. However, despite advances in trauma care management, mortality and complication rates remain high. Recently, systemic immune dysregulation and immunosuppression has been implicated as a main contributor to unsatisfactory success of intervention strategies and poor outcomes in a subset of trauma patients. The importance of the immune system in wound healing and tissue regeneration suggests that for optimal success of regenerative medicine strategies, this underlying systemic immune dysregulation must be addressed, highlighting a strong need for immunomodulatory approaches to augment regenerative therapies. This review addresses what is currently known about systemic immune dysregulation following severe trauma, previous attempts at immunomodulation, considerations for the development of future immunomodulatory strategies, and animal models for testing these therapeutics. The severity of immune dysregulation over time, both systemically and locally, is impacted by injury severity and patient-specific factors, such as age and co-morbidities. Varying degrees of systemic immune dysregulation may require different and personalized approaches to restore immune homeostasis. Further, the timing of treatment and the site of delivery must be considered to determine the most safe and effective intervention strategy. In order to test and develop these immunomodulatory therapeutics aimed at improving outcomes of regenerative interventions, robust pre-clinical models are needed that recapitulate systemic immune dysregulation and clinical scenarios. Overall, more fundamental research is needed to better understand the complex interactions between the musculoskeletal system and the immune system, as well as the importance of systemic and local immune function on healing. Ultimately, this information could lead to new immunomodulatory strategies to enhance regeneration for severe musculoskeletal trauma patients.

Endogenous cannabinoids (endocannabinoids, eCB) are expressed throughout the body and contribute to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and general stress reactivity. This study assessed the contributions of CB1 receptors (CB1R) in the modulation of basal and stress-induced neural and HPA axis activities. Catheterized adult male rats were placed in chambers to acclimate overnight, with their catheters connected and exteriorized from the chambers for relatively stress-free remote injections. The next morning, the CB1R antagonist AM251 (1 or 2 mg/kg) or vehicle was administered, and 30 min later, rats were exposed to loud noise stress (30 min) or no noise (basal condition). Blood, brains, pituitary and adrenal glands were collected immediately after the procedures for analysis of c-fos and CB1R mRNAs, corticosterone (CORT) and adrenocorticotropin hormone (ACTH) plasma levels. Basally, CB1R antagonism induced c-fos mRNA in the basolateral amygdala (BLA) and auditory cortex (AUD) and elevated plasma CORT, indicating disruption of eCB-mediated constitutive inhibition of activity. CB1R blockade also potentiated stress-induced hormone levels and c-fos mRNA in several regions such as the bed nucleus of the stria terminalis (BST), lateral septum (LS), and basolateral amygdala (BLA) and the paraventricular nucleus of the hypothalamus (PVN). CB1R mRNA was detected in all central tissues investigated, and the adrenal cortex, but at very low levels in the anterior pituitary gland. Interestingly, CB1R mRNA was rapidly and bidirectionally regulated in response to stress and/or antagonist treatment in some regions. eCBs therefore modulate the HPA axis by regulating both constitutive and activity-dependent inhibition at multiple levels.

Doxycycline is a tetracycline-class antimicrobial labeled by the U.S. Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline-class antibiotics and tooth staining, although doxycycline may be used off-label under severe conditions. Accordingly, there is a paucity of pharmacokinetic (PK) data to guide dosing in children 8 years and younger. We leveraged opportunistically collected plasma samples after intravenous (i.v.) and oral doxycycline doses received per standard of care to characterize the PK of doxycycline in children of different ages and evaluated the effect of obesity and fasting status on PK parameters. We developed a population PK model of doxycycline using data collected from 47 patients 0 to 18 years of age, including 14 participants ≤8 years. We developed a 1-compartment PK model and found doxycycline clearance to be 3.32 liters/h/70 kg of body weight and volume to be 96.8 liters/70 kg for all patients, comparable to values reported in adults. We estimated a bioavailability of 89.6%, also consistent with adult data. Allometrically scaled clearance and volume of distribution did not differ between children 2 to ≤8 years of age and children >8 to ≤18 years of age, suggesting that younger children may be given the same per-kilogram dosing. Obesity status and fasting status were not selected for inclusion in the final model. Additional doxycycline PK samples collected in future studies may be used to improve model performance and maximize its clinical value.

Background Given the rapid development during the early years (0-4 years), an understanding of the health implications of physical activity is needed. The purpose of this systematic review was to examine the relationships between objectively and subjectively measured physical activity and health indicators in the early years. Methods Electronic databases were originally searched in April, 2016. Included studies needed to be peer-reviewed, written in English or French, and meet a priori study criteria. The population was apparently healthy children aged 1 month to 59.99 months/4.99 years. The intervention/exposure was objectively and subjectively measured physical activity. The comparator was various volumes, durations, frequencies, patterns, types, and intensities of physical activity. The outcomes were health indicators ranked as critical (adiposity, motor development, psychosocial health, cognitive development, fitness) and important (bone and skeletal health, cardiometabolic health, and risks/harm). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of evidence for each health indicator by each study design. Results Ninety-six studies representing 71,291 unique participants from 36 countries were included. Physical activity interventions were consistently (>60% of studies) associated with improved motor and cognitive development, and psychosocial and cardiometabolic health. Across observational studies, physical activity was consistently associated with favourable motor development, fitness, and bone and skeletal health. For intensity, light- and moderate-intensity physical activity were not consistently associated with any health indicators, whereas moderate- to vigorous-intensity, vigorous-intensity, and total physical activity were consistently favourably associated with multiple health indicators. Across study designs, consistent favourable associations with health indicators were observed for a variety of types of physical activity, including active play, aerobic, dance, prone position (infants; ≤1 year), and structured/organized. Apart from ≥30 min/day of the prone position for infants, the most favourable frequency and duration of physical activity was unclear. However, more physical activity appeared better for health. Evidence ranged from “very low” to “high” quality. Conclusions Specific types of physical activity, total physical activity, and physical activity of at least moderate- to vigorous-intensity were consistently favourably associated with multiple health indicators. The majority of evidence was in preschool-aged children (3-4 years). Findings will inform evidence-based guidelines.

Objective Reinke's edema (RE) is a pathologically benign structural change of the vocal folds with a wide spectrum of clinical severity. We aim to propose and validate a clinical grading system based on size of the lesion to facilitate effective universal communication of disease severity. Study Design Retrospective review. Methods Patients diagnosed with RE exclusive of other glottic pathology between December 2010 and December 2014 were included. Sixty laryngoscopy photographs were extracted from recorded archived laryngeal videostroboscopy exams, blinded and graded by four laryngologists with experience diagnosing RE. Results A high degree of agreement among all four raters was demonstrated by high interclass correlation coefficients with a 95% confidence interval. Similarly, high intra-rater reliability was seen across all raters. Forty-nine (33%) lesions were grade 1. Thirty-five lesions (29.17%) were grade 2; 18 (15%) lesions were grade 3; and nine (7.5%) lesions were grade 4. Contralateral vocal fold was not graded in cases of grade 4. Conclusion This clinical grading for RE is a reliable tool for conveying severity of disease. High inter- and intra-rater reliability strongly suggest that RE similarly can be graded by different raters, and that a single rater is expected to grade RE similarly at different times. Level of Evidence 4. Laryngoscope, 127:2310–2313, 2017

The Brain Trauma Foundation guidelines provide indications for neurosurgical intervention in traumatic brain injury (TBI) with moderate or severe intracranial hemorrhage (ICH). In TBI patients with less severe ICH, the utility of neurosurgical consultation remains unclear. We sought to determine if routine neurosurgical consultation is necessary for mild blunt TBI patients with ICH. A retrospective cohort study was conducted on 500 consecutive blunt TBI patients aged 15 years or older with Glasgow Coma Scale score of ≥13 and ICH on initial head computed tomography admitted to a Level I trauma center over 28 months. Outcomes were neurosurgical intervention (craniotomy, craniectomy, ventriculostomy, or intracranial pressure monitor placement) and in-hospital mortality. Statistical significance was assessed at a p < 0.05. Of 500 patients, 49 (9.8%) underwent neurosurgical intervention. Neurosurgical intervention was more frequent in male patients (75.5% vs. 61.2%, p = 0.049), patients with higher head Abbreviated Injury Scale score (4.7 vs. 3.8, p < 0.0001), patients with an abnormal initial neurological examination (30.6% vs. 12.6%, p = 0.001), or patients with skull fracture (28.6% vs. 16.0%, p = 0.026) and was associated with higher mortality (8.2% vs. 2.0%, p = 0.010). Neurosurgical intervention was not associated with intoxication, preinjury antiplatelet/anticoagulation agents, or progression of ICH on second head computed tomography. Neurosurgical consultation was documented in 466 patients (93.2%). For patients without neurosurgical intervention, consultation did not change management. Routine neurosurgical consultation for blunt TBI with ICH seems unnecessary, regardless of intoxication or preinjury antiplatelet or anticoagulation therapy. A more selective approach is warranted to decrease hospital charges and optimize use of neurosurgical consultation. Care management study, level IV.

National-level data are limited regarding confidentiality-related issues and the use of sexually transmitted disease (STD) services for adolescents and young adults. Changes in the U.S. health care system have permitted dependent children to remain on a parent's health insurance plan until the child's 26th birthday and required coverage of certain preventive services, including some STD services, without cost sharing for most plans (1,2). Although these provisions likely facilitate access to the health care system, adolescents and young adults might not seek care or might delay seeking care for certain services because of concerns about confidentiality, including fears that their parents might find out (3,4). Therefore, it is important to examine STD services and confidentiality-related issues among persons aged 15-25 years in the United States. CDC analyzed data from the 2013-2015 National Survey of Family Growth and found that 12.7% of sexually experienced youths (adolescents aged 15-17 years and those young adults aged 18-25 years who were on a parent's insurance plan) would not seek sexual and reproductive health care because of concerns that their parents might find out. Particularly concerned were persons aged 15-17 years (22.6%). Females with confidentiality concerns regarding seeking sexual and reproductive health care reported a lower prevalence of receipt of chlamydia screening (17.1%) than did females who did not cite such concerns (38.7%). More adolescents aged 15-17 years who spent time alone with a health care provider (without a parent in the room) reported receipt of a sexual risk assessment (71.1%) and, among females, chlamydia testing (34.0%), than did those who did not spend time alone (36.6% and 14.9%, respectively). The results indicated that confidentiality-related issues were associated with less reported use of some STD services, especially for younger persons and females. Spending time alone with a provider (i.e., without a parent present) during a health care visit has been associated previously with higher reported delivery of sexual health services (5) and has been suggested by the American Academy of Pediatrics and Society for Adolescent Health and Medicine (6). Public health efforts related to confidentiality of STD services might be helpful to increase the use of recommended services among some youths.

To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P .001) and pervasive developmental problems (P .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values .05).BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burdens were due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among health care facilities. While CRKP was predicted to have been imported into each facility multiple times, there was substantial variation in the ratio of intrafacility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intrafacility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patients to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that patients colonized and infected with CRKP in high-transmission facilities had higher rates of carbapenem use, malnutrition, and dialysis and were older. This report highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify the patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.

Background The U.S. Preventive Services Task Force (USPSTF) recommends behavioral counseling for youth at high-risk for STDs, but little work has explored translation of these guidelines into practice. Here, we evaluated a large-scale implementation of behavioral counseling in federally qualified health centers (FQHCs). Methods Implementation occurred between June 2017 and May 2018 in four FQHCs in Northeastern US. Many patients were below the poverty level (27–65%) or uninsured (13–47%). Training content comprised motivational interviewing skills and techniques for talking to youth about sex and sexual histories, delivered to pilot providers via 15 hours of online and in-person training. We measured the proportion of patients who received (a) a sexual history, (b) behavioral counseling, (c) HPV vaccine and (d) chlamydia screening. We tracked changes in work-flow and implementation and allowed for tailoring of sexual history taking per the needs of FQHCs. Results 39,631 eligible patients (13–24 years old, 71.0% Hispanic, 68.3% white, 24.9% black) were seen during the implementation period, of whom 9,675 (24.4%) saw a pilot provider. Similar proportions in each group completed a sexual history (70.6% vs. 71.4%, p=0.1787). However, higher proportions of patients exposed to the pilot providers received behavioral counseling (67.5% vs. 43.5%, p Conclusion Primary outcomes from this translation study support the conclusion that an intensive, but short, training regimen on behavioral counseling, coupled with a flexible strategy for assessing sexual histories, results in higher rates of behavioral counseling and provision of prevention services as compared to those who did not receive training. Disclosure No significant relationships.

Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of critical illness. We developed a population pharmacokinetic model of milrinone using nonlinear mixed-effects modeling in NONMEM to perform dose-exposure simulations in children with variable renal function. We included children aged

Reports indicate that long-term opioid therapy is associated with cardiovascular disease (CVD). Using VA electronic health record data, we measured the impact of opioid use on the incidence of modifiable CVD risk factors. We included Veterans whose encounter was between October 2001 to November 2014. We identified Veterans without CVD risk factors during our baseline period, defined as the date of first primary care visit plus 365 days. The main exposure was opioid prescriptions (yes/no, long-term (i.e. ≥90 days) vs no opioid, and long-term vs short-term (i.e.90 days)), which was time-updated yearly from the end of the baseline period to February 2015. The main outcome measures were incident CVD risk factors (hypertension, dyslipidemia, diabetes, obesity, and current smoking). After excluding prevalent CVD risk factors, we identified 308,015 Veterans. During the first year of observation, 12,725 (4.1%) Veterans were prescribed opioids, including 2028 (0.6%) with long-term exposure. Compared to patients without opioid use, Veterans with opioid use were more likely to have CVD risk factors. Those with long-term exposure were at higher risk of having hypertension (adjusted average hazards ratio [HR] 1.45, 99% confidence interval [CI] 1.33-1.59), dyslipidemia (HR 1.45, 99% CI 1.35-156), diabetes (HR 1.30, 99% CI 1.07-1.57), current smoking status (HR 1.34, 99% CI 1.24-1.46), and obesity (HR 1.22, 99% CI 1.12-1.32). Compared to short-term exposure, long-term had higher risk of current smoking status (HR 1.12, 99% CI 1.01-1.24). These findings suggest potential benefit to screening and surveillance of CVD risk factors for patients prescribed opioids, especially long-term opioid therapy.

Prenatal exome sequencing (ES) currently has limited use in the clinical setting, but research suggests that it has added diagnostic utility over karyotyping and array techniques for prenatal diagnosis of fetuses presenting with ultrasound abnormalities. The purpose of this study was to assess the attitudes of genetics professionals toward the clinical implementation of prenatal ES in order to guide development of professional guidelines. A survey was developed using themes identified in previous qualitative studies and was distributed to members of the American College of Medical Genetics and Genomics (ACMG), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC). A total of 498 participants completed some portion of the survey. There was consensus among participants that there would be clinical utility of prenatal ES when used for diagnosis, pregnancy management, and termination decisions. The majority also agreed that prenatal ES was distinct from its current use in the pediatric and adult settings. There were many areas of contention regarding which types of results should be returned to families and whether or not the current ACMG guidelines for return of incidental findings should also apply to the prenatal setting. Overall, professional guidance is needed to address the continuing concerns surrounding prenatal ES as its utilization in this setting is expected to grow.

AIMS: Patients with heart failure often have under-recognized symptoms, depression, anxiety, and poorer spiritual well-being (‘QoL domains’). Ideally all patients should have heart failure-specific health status and quality of life (QoL) domains routinely evaluated; however, lack of time and resources are limiting in most clinical settings. Therefore, we aimed to evaluate whether heart failure-specific health status was associated with QoL domains and to identify a score warranting further evaluation of QoL domain deficits. METHODS AND RESULTS: Participants (N = 314) enrolled in the Collaborative Care to Alleviate Symptoms and Adjust to Illness trial completed measures of heart failure-specific health status [Kansas City Cardiomyopathy Questionnaire, KCCQ (score 0–100, 0 = worst health status)], additional symptoms (Memorial Symptom Assessment Scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), and spiritual well-being (Facit-Sp) at baseline. Mean ± standard deviation (SD) KCCQ score was 46.9 ± 19.3, mean age was 65.5 ± 11.4, and 79% were male. Prevalence of QoL domain deficits ranged from 11% (nausea) to 47% (depression). Sensitivity/specificity of KCCQ for each QoL domain ranged from 20–40%/80–96% for KCCQ ≤ 25, 61–84%/48–62% for KCCQ ≤ 50, 84–97%/26–40% for KCCQ ≤ 60, and 96–100%/8–13% for KCCQ ≤ 75. Patients with KCCQ ≤ 60 had mean ± SD 4.5 ± 2.5 QoL domain deficits (maximum 12), vs. 1.6 ± 1.6 for KCCQ > 60 (P

ObjectiveTo perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics.DesignSystematic review with random-effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcomes (FHR, beats per minute (bpm); uterine and umbilical blood flow metrics (systolic:diastolic (S/D) ratio; Pulsatility Index (PI); Resistance Index (RI); blood flow, mL/min; and blood velocity, cm/s)).Results‘Very low’ to ‘moderate’ quality evidence from 91 unique studies (n=4641 women) were included. Overall, FHR increased during (mean difference (MD)=6.35bpm; 95% CI 2.30 to 10.41, I2=95%, p=0.002) and following acute exercise (MD=4.05; 95% CI 2.98 to 5.12, I2=83%, pConclusionAcute and chronic prenatal exercise do not adversely impact FHR or uteroplacental blood flow metrics.