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Little information is known about the cisgender women who seek and initiate pre-exposure prophylaxis (PrEP) for HIV prevention in the United States. Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week single-arm open-label demonstration study of daily oral tenofovir disoproxil fumaratel emtricitabine (TDF/FTC) in cisgender women ≥ 18 years old at risk for HIV. Participants were surveyed at screening and enrollment about sociodemographics, HIV risk perception and behaviors, and PrEP perspectives and aggregated into three risk groups according to HIV sexual risk behavior: being in a serodiscordant partnership (SD), engaging in sex work (SW), and having partners with unknown HIV status at risk for HIV (UP). One hundred sixty-seven women presented for screening with n = 31 screen failures. Of the 162 women completing enrollment, mean age was 40 (standard deviation 11), with 41% non-Hispanic Black, 22% non-Hispanic White, and 19% Latina. Compared with those who screened ineligible, enrolled participants were more likely to have heard of PrEP, had higher HIV risk perception, and reported higher perceived PrEP efficacy. Sixty-four women (47%) were categorized as SD, 21 (15%) as SW, and 51 (38%) as UP. The SW were more likely to report higher levels of drinking and drug use (p = 0.002) and history of intimate partner violence in the past year (p < 0.001) compared with SD and UP. Among cisgender women enrolled, there were significant differences between the three risk groups by demographics, HIV risk behavior, and PrEP perspectives, suggesting that interventions to successfully implement PrEP in US women may need to be tailored by HIV risk group. Clinical Trial Registration number: NCT02584140. [ABSTRACT FROM AUTHOR]

Summary: Background: Economic development has brought rapid shifts in the food environment of Chinese children and adolescents. Objectives: To assess the changes in childhood nutritional status across ethnic groups and economic status from 2005 to 2014. Methods: 664 094 Chinese Han and 224 151 ethnic minority children and adolescents aged 7 to 18 years were assessed in three national cross‐sectional surveys (2005, 2010 and 2014). Gross domestic product (GDP) per capita of each ethnic group was categorized into four strata of socioeconomic status. To assess ethnic disparities at each time point, we used logistic regression to estimate the prevalence odds ratios (OR) for thinness, overweight and obesity in the 24 ethnic minority groups vs Han Chinese. Results: Children in the two upper economic strata (over about US$4000 GDP per capita) had a high prevalence of overweight and obesity, while those in the two lower economic strata (below US$4000 GDP per capita) had a high prevalence of thinness. From 2005 to 2014, the prevalence of thinness decreased from 18.6% to 13.1% in Han children, and from 20.4% to 17.1% in ethnic minority students. At the same time, the prevalence of overweight and obesity increased from 10.4% to 17.7% in Han children, and from 4.3% to 9.2% in ethnic minority students, respectively. Conclusions: A rapid nutritional transition has occurred from 2005 to 2014 with shifts from thinness to overweight and obesity in both Han and ethnic minority children and adolescents, reflecting local GDP per capita. [ABSTRACT FROM AUTHOR]

Background Problem drinking that predates enlistment into military service may contribute to the overall burden of alcohol misuse in the Armed Forces; however, evidence bearing on this issue is limited. This study examines prevalence and correlates of alcohol misuse among new U.S. Army soldiers. Methods Cross-sectional survey data were collected from soldiers reporting for basic combat training. The survey retrospectively assessed lifetime alcohol consumption and substance abuse/dependence, enabling estimation of the prevalence of lifetime binge drinking and heavy drinking in a sample of 30,583 soldiers and of probable alcohol use disorder ( AUD) among 26,754 soldiers with no/minimal lifetime use of other drugs. Co-occurrence of mental disorders and other adverse outcomes with binge drinking, heavy drinking, and AUD was examined. Discrete-time survival analysis, with person-year the unit of analysis and a logistic link function, was used to estimate associations of AUD with subsequent onset of mental disorders and vice versa. Results Weighted prevalence of lifetime binge drinking was 27.2% ( SE = 0.4) among males and 18.9% ( SE = 0.7) among females; respective estimates for heavy drinking were 13.9% ( SE = 0.3) and 9.4% ( SE = 0.4). Among soldiers with no/minimal drug use, 9.5% ( SE = 0.2) of males and 7.2% ( SE = 0.5) of females had lifetime AUD. Relative to no alcohol misuse, binge drinking, heavy drinking, and AUD were associated with increased odds of all mental disorders and other adverse outcomes under consideration (adjusted odds ratios [ AORs] = 1.5 to 4.6; ps < 0.001). Prior mental disorders and suicidal ideation were associated with onset of AUD ( AORs = 2.3 to 2.8; ps < 0.001), and prior AUD was associated with onset of mental disorders and suicidal ideation ( AORs = 2.0 to 3.2, ps < 0.005). Conclusions Strong bidirectional associations between alcohol misuse and mental disorders were observed in a cohort of soldiers beginning Army service. Conjoint recognition of alcohol misuse and mental disorders upon enlistment may provide opportunities for risk mitigation early in a soldier's career. [ABSTRACT FROM AUTHOR]

Background: The US Food and Drug Administration (FDA) proposed 2- and 10-year voluntary sodium-reduction targets for >150 packaged- and prepared-food categories in 2016 and finalized the short-term targets in 2021., Methods: We modeled the health benefits of implementing the newly finalized sodium targets, and the net health losses because of the 4.3-year delay in finalizing the sodium targets in different compliance scenarios in adults aged ≥30, using the National Health and Nutrition Examination Survey (NHANES) 2015 to 2016 cycle. The health impact was estimated by multiplying the projected reduction in population sodium intake by the annual health benefits resulting from every 1000-mg reduction in daily sodium intake., Results: Under certain assumptions, the FDA's finalization of the short-term targets in Oct 2021 and possible finalization of the long-term targets by April 2024 is projected to save up to 445 979 (95% CI, 17 349-787 352) lives in the coming 10 years. The net number of unnecessary deaths because of FDA's delay is projected to be as high as 264 644 (95% CI, 10 295-467 215) according to our prediction., Conclusions: These findings highlight the enormous health costs due to the FDA's delay in finalizing the sodium-reduction targets, and the great potential health benefits of industry compliance with the FDA's finalization of its short- and long-term targets in the coming 10 years.

Background: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease., Methods: In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244., Findings: Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13-0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only., Interpretation: Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion., Funding: Patient Centered Outcomes Research Institute., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension., Research Question: What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects?, Study Design and Methods: This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019., Results: Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001)., Interpretation: Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women., Methods: Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week, single-arm, open-label demonstration study of daily oral TDF/FTC in cisgender women ≥18 years old at risk for HIV. Adherence was supported using 2-way text messaging and titrated adherence counseling based on rapid-turnaround tenofovir diphosphate concentrations from dried blood spots. Study visits occurred at baseline, weeks 4 and 12, and quarterly through week 48. Outcomes included TDF/FTC adherence, retention, and persistence., Results: From June 2016 to October 2018, 136 cisgender women enrolled (mean age, 40 years (standard deviation, 11); 38% non-Hispanic Black and 19% Latina). At 48 weeks, 84 (62%) participants were retained and 62 (46%) remained on PrEP. More than one-third (12/31) of those on study but off PrEP throughout the study discontinued TDF/FTC because of side effects, and 1 adverse event led to study discontinuation. Of 120 participants with drug concentrations measured, 67 (56%) had at least 1 concentration consistent with 6 doses/week; 22 (18%) had consistent ≥6 doses/week across all study visits attended. There were no incident HIV infections and 4 incident bacterial sexually transmitted infections., Conclusion: Adequate PrEP adherence for protective drug concentrations was not achieved for most study participants. More work needs to be done to fully explicate the reasons for nonadherence and low retention in cisgender women., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Anxiety disorders (ANX), namely generalized anxiety, panic disorder, and phobias, are common, etiologically complex syndromes that show increasing prevalence and comorbidity throughout adolescence and beyond. Few genome-wide association studies (GWAS) examining ANX risk have been published and almost exclusively in individuals of European ancestry. In this study, we phenotyped participants from the Army Study To Assess Risk and Resilience in Servicemembers (STARRS) to approximate DSM-based ANX diagnoses. We factor-analyzed those to create a single dimensional anxiety score for each subject. GWAS were conducted using that score within each of three ancestral groups (EUR, AFR, LAT) and then meta-analyzed across ancestries (N Total = 16,510). We sought to (a) replicate prior ANX GWAS findings in ANGST; (b) determine whether results extended to other ancestry groups; and (c) meta-analyze with ANGST for increased power to identify novel susceptibility loci. No reliable genome-wide significant SNP associations were detected in STARRS. However, SNPs within the CAMKMT gene located in region 2p21 associated with shared ANX risk in ANGST were replicated in EUR soldiers but not other ancestry groups. Combining EUR STARRS and ANGST (N = 28,950) yielded a more robust 2p21 association signal (p = 9.08x10 -11 ). Gene-based analyses supported three genes within 2p21 and LBX1 on chromosome 10. More powerful ANX genetic studies will be required to identify further loci., (© 2019 Wiley Periodicals, Inc.)

Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome-wide association studies (GWASs) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self-assessed resilience (N = 11,492) was found to have significant common-variant heritability (h 2 = 0.162, se = 0.050, p = 5.37 × 10 -4 ), and to be significantly negatively genetically correlated with neuroticism (r g  = -0.388, p = .0092). GWAS results from the EUR soldiers revealed a genome-wide significant locus on an intergenic region on Chr 4 upstream from doublecortin-like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [p = 5.65 × 10 -9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch-like family member 36 (KLHL36) was detected at gene-wise genome-wide significance [p = 1.89 × 10 -6 ]. A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genome-wide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015 [p = 2.37 × 10 -8 ]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects (N = 581) exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress-related psychopathology and point to new avenues for therapeutic intervention., (© 2019 Wiley Periodicals, Inc.)

In 2015, ~800,000 people died by suicide worldwide. For every death by suicide there are as many as 25 suicide attempts, which can result in serious injury even when not fatal. Despite this large impact on morbidity and mortality, the genetic influences on suicide attempt are poorly understood. We performed a genome-wide association study (GWAS) of severity of suicide attempts to investigate genetic influences. A discovery GWAS was performed in Yale-Penn sample cohorts of European Americans (EAs, n = 2,439) and African Americans (AAs, n = 3,881). We found one genome-wide significant (GWS) signal in EAs near the gene LDHB (rs1677091, p = 1.07 × 10 -8 ) and three GWS associations in AAs: ARNTL2 on chromosome 12 (rs683813, p = 2.07 × 10 -8 ), FAH on chromosome 15 (rs72740082, p = 2.36 × 10 -8 ), and on chromosome 18 (rs11876255, p = 4.61 × 10 -8 ) in the Yale-Penn discovery sample. We conducted a limited replication analysis in the completely independent Army-STARRS cohorts. rs1677091 replicated in Latinos (LAT, p = 6.52 × 10 -3 ). A variant in LD with FAH rs72740082 (rs72740088; r 2  = 0.68) was replicated in AAs (STARRS AA p = 5.23 × 10 -3 ; AA meta, 1.51 × 10 -9 ). When combined for a trans-population meta-analysis, the final sample size included n = 20,153 individuals. Finally, we found significant genetic overlap with major depressive disorder (MDD) using polygenic risk scores from a large GWAS (r 2  = 0.007, p = 6.42 × 10 -5 ). To our knowledge, this is the first GWAS of suicide attempt severity. We identified GWS associations near genes involved in anaerobic energy production (LDHB), circadian clock regulation (ARNTL2), and catabolism of tyrosine (FAH). These findings provide evidence of genetic risk factors for suicide attempt severity, providing new information regarding the molecular mechanisms involved.

Objective: Understanding suicide risk is a priority for the US military. We aimed to estimate associations of childhood maltreatment with pre-enlistment suicidal behaviors in new Army soldiers., Methods: Cross-sectional survey data from 38,237 soldiers reporting for basic training from April 2011 through November 2012 were analyzed. Scales assessing retrospectively reported childhood abuse and neglect were derived and subjected to latent class analysis, which yielded 5 profiles: No Maltreatment, Episodic Emotional Maltreatment, Frequent Emotional/Physical Maltreatment, Episodic Emotional/Sexual Abuse, and Frequent Emotional/Physical/Sexual Maltreatment. Discrete-time survival analysis was used to estimate associations of maltreatment profiles with suicidal behaviors (assessed with a modified Columbia-Suicide Severity Rating Scale), adjusting for sociodemographics and mental disorders., Results: Nearly 1 in 5 new soldiers was classified as experiencing childhood maltreatment. Relative to No Maltreatment, all multivariate maltreatment profiles were associated (P values < .001) with elevated odds of lifetime suicidal ideation (adjusted odds ratios [AORs] = 3.10-4.93), plan (AORs = 3.75-10.77), attempt (AORs = 3.60-15.95), and onset of plan among those with ideation (AORs = 1.40-3.10). Several profiles also predicted attempts among those with plans (AORs = 2.01-2.47), and Frequent Emotional/Physical/Sexual Maltreatment predicted unplanned attempts among ideators (AOR = 5.32). Adjustment for mental disorders attenuated but did not eliminate these associations., Conclusions: Childhood maltreatment is strongly associated with suicidal behavior among new soldiers, even after adjusting for intervening mental disorders. Among soldiers with lifetime ideation, certain maltreatment profiles are associated with elevated odds of subsequently planning and/or attempting suicide. Focus on childhood maltreatment might reveal avenues for risk reduction among new soldiers., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Objective: The concept of symptom clusters is relatively new in cancer patients' symptom management. This study, which spanned four cycles of chemotherapy, combined three commonly seen pre-treatment symptoms in cancer patients (i.e. sleep disturbances, fatigue and depression) into one symptom cluster, to explore the associations between pre-treatment cluster categories and longitudinal profiles of these same symptoms during chemotherapy., Methods: This was a prospective study. Seventy-six women with newly diagnosed stage I-III breast cancer, scheduled to receive at least four cycles of adjuvant or neoadjuvant anthracycline-based chemotherapy participated. Data were collected at seven time points before and during treatment. Sleep quality was measured with the Pittsburgh Sleep Quality Index. Fatigue was measured with the Multidimensional Fatigue Symptom Inventory--Short Form. Depressive symptoms were measured with the Center of Epidemiological Studies--Depression. Patients were divided into three groups based on the number of symptoms they experienced before the start of chemotherapy (i.e. no symptoms, 1-2 symptoms or all three symptoms) and a symptom cluster index (SCI) was computed., Results: All women reported worse sleep, more fatigue and more depressive symptoms during treatment compared with baseline (all p's<0.01); however, those women with a higher SCI (i.e. more symptoms pre-treatment) continued to experience worse symptoms during treatment compared with those who began with fewer symptoms (all p's<0.01)., Conclusions: A higher clinically relevant-based pre-treatment symptom cluster was associated with more sleep disturbances, greater fatigue and more depressive symptoms during chemotherapy. Specific interventions for these pre-treatment symptoms may improve the frequency and severity of these same symptoms during chemotherapy, when they are most severe and most disruptive to quality of life., ((c) 2008 John Wiley & Sons, Ltd.)