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This report describes the Ion Endoluminal System (Intuitive Surgical, Inc, Sunnyvale, CA) and practices for safe and effective use in patients with small peripheral pulmonary nodules (PPNs).This shape-sensing robotic-assisted bronchoscopy system allows airway visualization and navigation to reach and biopsy small PPNs through a stable platform. The system provides 3-dimensional mapping and visualization of the airways, a flexible and fully articulating 3.5-mm (outer diameter) catheter, a peripheral vision probe, and system-specific biopsy needles.The Ion Endoluminal System was evaluated in an ongoing prospective, multicenter trial including 241 patients with 270 PPNs (largest mean cardinal measurement, 18.8 ± 6.5 mm). Mean time to register and navigate decreased from 10 minutes in the first 10 cases to 7 minutes in the subsequent cases. Asymptomatic pneumothorax occurred in 8 patients (3.3%), 1 (0.4%) with pigtail catheter placement. Two patients (0.8%) experienced airway bleeding; both cases of bleeding resolved within 5 minutes of tamponade.The Ion Endoluminal System's unique shape-sensing technology can be leveraged to facilitate localization and sampling of PPNs and potentially improve diagnostic accuracy.

For patients with lupus erythematosus (LE) or dermatomyositis (DM), there is an urgent need to address a heightened risk of clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). Patients with LE or DM frequently exhibit high levels of conventional risk factors for ASCVD events, particularly dyslipoproteinemia and hypertension; an amplified burden of atherosclerotic plaques; and increased age- and sex-adjusted rates of ASCVD events compared with the general population. The rate of ASCVD events exceeds what would be expected from conventional risk factors, suggesting that disease-specific autoimmune processes exacerbate specific, known pathogenic steps in atherosclerosis. Importantly, despite their heightened risk, patients with LE or DM are often undertreated for known causative agents and exacerbators of ASCVD. Herein, we propose an approach to assess and manage the heightened risk of ASCVD events in patients with LE or DM. Our approach is modeled in large part on established approaches to patients with diabetes mellitus or stage 3 or 4 chronic kidney disease, which are well-studied conditions that also show heightened risk for ASCVD events and have been explicitly incorporated into standard clinical guidelines for ASCVD. Based on the available evidence, we conclude that patients with LE or DM require earlier and more aggressive screening and management of ASCVD. We suggest that physicians consider implementing multipliers of conventional risk calculators to trigger earlier initiation of lifestyle modifications and medical therapies in primary prevention of ASCVD events, employ vascular imaging to quantify the burden of subclinical plaques, and treat to lower lipid targets using statins and newer therapies, such as PCSK9 inhibitors, that decrease ASCVD events in nonautoimmune cohorts. More clinical vigilance is needed regarding surveillance, prevention, risk modification, and treatment of dyslipidemias, hypertension, and smoking in patients with LE or DM. All of these goals are achievable.

Background: Previous studies of the effect of interaction between psychiatric disorders on suicide have reported mixed results. We investigated the joint effect of depression and various comorbid psychiatric disorders on suicide. Methods: We conducted a population-based case–cohort study with all suicide deaths occurring between 1 January 1995 and 31 December 2015 in Denmark (n = 14,103) and a comparison subcohort comprised of a 5% random sample of the source population at baseline (n = 265,183). We quantified the joint effect of pairwise combinations of depression and major psychiatric disorders (e.g., organic disorders, substance use disorders, schizophrenia, bipolar disorder, neurotic disorders, eating disorders, personality disorders, intellectual disabilities, developmental disorders, and behavioral disorders) on suicide using marginal structural models and calculated the relative excess risk due to interaction. We assessed for the presence of competing antagonism for negative relative excess risk due to interactions. Results: All combinations of depression and comorbid psychiatric disorders were associated with increased suicide risk. For example, the rate of suicide among men with depression and neurotic disorders was 20 times (95% CI = 15, 26) the rate in men with neither disorder. Most disorder combinations were associated with subadditive suicide risk, and there was evidence of competing antagonism in most of these cases. Conclusions: Subadditivity may be explained by competing antagonism. When both depression and a comorbid psychiatric disorder are present, they may compete to cause the outcome such that having 2 disorders may be no worse than having a single disorder with respect to suicide risk.

Objectives. To determine whether there have been shifts in nonmedical ketamine use, poisonings (“exposures”), and seizures. Methods. We used generalized additive models to detect trends in past-year use (2006–2019), exposures (1991–2019), and seizures (2000–2019) involving ketamine in the United States. Results. There was a quarterly increase in self-reported past-year nonmedical ketamine use in 2006 to 2014 (Β = 0.21; P = .030) and an increase in 2015 to 2019 (Β = 0.29; P = .036), reaching a peak of 0.9% in late 2019. The rate of exposures increased from 1991 through 2019 (Β = 0.87; P = .006), and there was an increase to 1.1 exposures per 1 000 000 population in 2014, with rates remaining stable through 2019. The rate of ketamine seizures increased from 2000 through 2019 (Β = 2.27; P Conclusions. Indicators suggest that ketamine use and availability has increased, including before increased medical indications, but nonmedical use is still currently uncommon despite increased acceptance and media coverage. (Am J Public Health. 2021;111(11):2046–2049. https://doi.org/10.2105/AJPH.2021.306486 )

Purpose We aimed to estimate the structure of internalizing and externalizing symptoms and potential time dynamics in their association. This is understudied among adolescents, despite increasing internalizing and decreasing externalizing symptoms in recent years. Methods We analyzed data from US Monitoring the Future cross-sectional surveys (1991–2018) representative of school-attending adolescents (N = 304,542). Exploratory factor analysis using maximum likelihood estimation method and promax rotation resulted in a two-factor solution (factor correlation r = 0.24) that differentiated eight internalizing and seven conduct-related externalizing symptoms. Time-varying effect modification linear regression models estimated the association between standardized internalizing and externalizing symptoms factor scores over time overall and by gender. Results In 2012, trends in average factor scores diverged for internalizing and externalizing factors. The average standardized internalizing factor score increased from − 0.03 in 2012 to 0.06 in 2013 and the average externalizing factor score decreased from − 0.06 in 2011 to − 0.13 in 2012. We found that for every one-unit increase in standardized internalizing factor score, standardized externalizing factor score increased by 0.224 units in 2010 (95% CI: 0.215, 0.233); the magnitude of this increase was 22.3% lower in 2018 (i.e., 0.174 units; 95% CI: 0.160, 0.188). Decoupling of internalizing and externalizing symptoms began earlier among boys (~ 1995) than among girls (~ 2010). Conclusion The decoupling of internalizing and externalizing symptoms among adolescents suggests that changes in the prevalence of shared risk factors for adolescent psychiatric symptoms affect these dimensions in opposing directions, raising the importance of considering symptoms and their risk factors together in prevention and intervention efforts. Supplementary Information The online version contains supplementary material available at 10.1007/s00127-021-02189-4.

Background Emergency department visits due to head injury in the United States have increased significantly over the past decade, and parallel the increasing use of direct oral anticoagulants (DOACs). Objective We investigated the incidence of delayed intracranial hemorrhage (DICH) in patients with head injury who were taking DOACs. Methods We conducted a single-center retrospective study at a level II trauma center. All patients with head injury and using DOACs with an initial negative head computed tomography (HCT) scan from March 1, 2014 to December 31, 2017 were included. DICH was identified as a positive finding on repeat HCT performed within 24 h. Each case of DICH underwent blinded review by two additional neuroradiologists. Demographic data were collected; independent t-tests were used to compare group means and linear regression for variable correlations. Results Two hundred and eighty-seven patients with mean age of 80 years (interquartile range 14 years) met inclusion criteria. Repeat HCT was performed in 224 study participants (78%). Five (1.7%) resulted in DICH, three of which might have been present on initial HCT, with an incidence rate ranging from 0.7% to 1.7%. Only two initial HCTs were read as negative by all three neuroradiologists; 60% disagreed on the initial read. Independent t-test procedures showed an association between DICH and higher Injury Severity Score (ISS). Conclusions We found a DICH incidence rate of 0.7–1.7%. ISS was statistically significant between the two groups. It is possible that in patients with a subjective estimation of low injury severity, a low mechanism of injury and reasonable outpatient follow-up, patients can be discharged home with standard head injury precautions and no repeat HCT, but further prospective studies are needed.

Background Binge drinking among adolescents and young adults has changed over time, but patterns differ by age and gender. Identifying high-risk groups to target future efforts at reducing drinking in this population remains a public health priority. Forecasting methods can provide a better understanding of variation and determinants of future binge drinking prevalence. Methods We implemented regression-based forecasting models to estimate the prevalence and gender differences in binge drinking among cohort groups of U.S. young adults, ages 18, 23-24, and 29-30 through 2040. Forecasting models were adjusted for covariates accounting for changes in demographic, Big-5 social roles (e.g., residential independence), and drinking norms and related substance use, to understand the drivers of forecasted binge drinking estimates. Results From the last observed cohort group (years varied by age) through 2040, unadjusted binge drinking prevalence was forecasted to decrease from 26% (95% CI: 20, 33%) (2011-15) to 11% (95% CI: 4, 27%) at age 18, decrease from 38% (95% CI: 30, 45%) (2006-2010) to 34% (95% CI: 18, 55%) at ages 23/24, and increase from 32% (95% CI: 25, 40%) (2001-2005) to 35% (95% CI: 16, 59%) at ages 29/30. Gender-stratified forecasts show a continuation in the narrowing of binge drinking prevalence between young men and women, though the magnitude of narrowing differs by age. Estimated trends were partially explained by changing norms regarding drinking and other substance use, though these indirect effects explained less of the total trend as age increased. Conclusions Understanding how covariates influence binge drinking trends can guide public health policies to leverage the most important determinants of future binge drinking to reduce the harm caused by binge drinking from adolescence to adulthood.

Dermatomyositis is a multisystem autoimmune connective tissue disease that can manifest with proximal muscle weakness, interstitial lung disease, and characteristic skin findings such as erythema and papules over the dorsal joints of the hand, periungual changes, heliotrope rash, and pruritic erythematous inflammation of the chest, back, arms, legs, and scalp. Erythromelalgia is a clinical diagnosis characterized by swelling, erythema, and burning pain, typically of the extremities and often triggered by heat or exertion. It can be classified as primary, due to genetic mutations, or secondary, associated with myeloproliferative, vascular, musculoskeletal, or neurologic disease.1 There have been reports of biopsies of erythromelalgia having some features of connective tissue disease.2,3 There are also reports of erythromelalgia associated with systemic lupus erythematosus and rheumatoid arthritis, two autoimmune connective tissue diseases.4 Here, we present two cases of erythromelalgia associated with dermatomyositis, which, to our knowledge, has not been reported in the literature to date. Case 1 An 81-year-old woman with a history of treated breast cancer presented to the dermatology clinic for evaluation of swelling and discoloration of her bilateral hands and feet of approximately 10 years' duration associated with heat intolerance. She had been seen by numerous vascular and lymphedema specialists over the years with the ultimate conclusion that her swelling was not associated with a vascular etiology. The patient noticed improvement of her symptoms when she was exposed to air conditioning or cold water. At presentation, she also reported shortness of breath, a burning sensation on her feet and scalp, subjective proximal muscle weakness, dysphagia, and weight gain. Her physical examination was notable for periungual telangiectasias, scale, and erythema on the V of her neck area, her extensor arms, and around her eyes (Fig 1). She believed that the erythema on the V of her neck area started 30 years ago, indicating the possibility that she had had potentially undiagnosed amyopathic dermatomyositis (DM) for years before her diagnosis of erythromelalgia. The patient's basic laboratory workup and immunologic studies were unrevealing, and a myositis panel was negative. Muscle magnetic resonance imaging and electromyography were not performed because of the absence of muscle pain or objective weakness on physical examination. Two skin biopsy specimens from the upper portion of the arm and the dorsal surface of the hand showed interface dermatitis (Fig 2), consistent with a diagnosis of DM based on clinicopathologic correlation with typical features of DM (as opposed to lupus, drug reaction, viral exanthem, lichen planus, or graft versus host disease). Pulmonary function testing showed an obstructive pattern with decreased carbon monoxide diffusion in the lung (62%), and chest computed tomography (CT) showed stable interstitial lung changes. The malignancy workup (including age-appropriate screening and CT of the chest, abdomen, and pelvis) was negative. The patient has had some relief from the burning sensation on her feet from topical 5% lidocaine and petroleum jelly. Because of shared decision-making and risk-benefit analysis, the patient has not started immunosuppressive therapy for her DM, but she is being followed closely. Open in a separate window Fig 1 Patient 1. Swelling and erythema on bilateral hands and feet.

We have an academic medical center (AMC), an associated community-based hospital (CBH) and several ambulatory care centers which are being prepared to provide same day discharge (SDD) total joint arthroplasty (TJA) and unicompartmental knee arthroplasty (UKA). The near-capacity AMC cared for medically and technically complicated TJA patients. The CBH wanted to increase volume, improve margins, and become a center of excellence with an efficient hospital outpatient department and SDD TJA experience. Methods We transitioned primary, uncomplicated TJA, UKA, and minimally invasive TJA to the CBH. Revision surgeries, patients with extensive comorbidities, and complex primaries were performed at the AMC. Protocols were developed to facilitate SDD UKA and total hip arthroplasty (THA) as well as rapid recovery protocols for total knee arthroplasty (TKA) at both hospitals. A protocol-based system was put in place to make both hospitals ready for the removal of TKA from the Inpatient-Only list to avoid Quality Improvement Organization and possible resultant Recovery Audit Contractor audits if referred after implementation. Results The CBH volume increased 36.7% (+239). AMC volume slightly decreased (−0.46%, −5) resulting in an increase in margin contribution for the system. CBH quality metrics (surgical site infections, length of stay, readmissions, and mortality) were improved. Surgeon satisfaction improved as their volume, efficiency, quality metrics, and finances were enhanced. Although CBH per case revenue was 80.3% and 74.4% of the AMC for THA and TKA, net margins were 3.6% and 18.8% higher for THA and TKA, respectively. Increased efficiency, lower hospital cost, and higher volume at the CBH allowed for an increase in revenue despite lower reimbursement per case. Conclusion This strategy will help hospital systems improve net margins while improving patient care despite lower net revenue per TJA episode. These strategies will become increasingly important going forward with the transition of higher numbers of TJA patients to outpatient which will be subjected to further decreases in net revenue per patient.

Over the past decade, US adolescents' depressive symptoms have increased, and changing religious beliefs and service attendance may be contributing factors. We examined the contribution of religious factors to depressive symptoms among 417,540 US adolescents (grades: 8, 10, 12), years:1991-2019, in survey-weighted logistic regressions. Among adolescents who felt religion was personally important, those who never attended services had 2.23 times higher odds of reporting depressive symptoms compared to peers attending weekly. Among adolescents who did not feel that religion was important, the pattern was reversed. Among adolescents, concordance between importance of religion and religious service attendance may lower risk of depressive symptoms. Overall, we estimate that depressive symptom trends would be 28.2% lower if religious factors had remained at 1991 levels.

Dermatomyositis (DM) is a rare inflammatory disorder commonly manifesting with proximal muscle weakness and characteristic skin findings. Classic findings include erythematous papules or macules over the small joints of the hand, periungual changes, pruritic/erythematous skin on areas including the scalp, chest, upper back, and other surfaces, as well as interstitial lung disease. Anasarca1 and chronic hyponatremia2 have rarely been reported in cases of DM, and have only been reported separately. Here, we present a case of dermatomyositis associated with both anasarca and hyponatremia.

Rationale: Systemic sclerosis (SSc)–pulmonary arterial hypertension (PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis. Objectives: We investigated the safety and efficacy of B-cell depletion for SSc-PAH. Methods: In an NIH-sponsored, multicenter, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 patients with SSc-PAH on stable-dose standard medical therapy received two infusions of 1,000 mg rituximab or placebo administered 2 weeks apart. The primary outcome measure was the change in 6-minute-walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug responsiveness. Measurements and Main Results: We randomized 57 subjects from 2010 to 2018. In the primary analysis, using data through Week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6 ± 11.1 m vs. 0.5 ± 9.7 m; P = 0.12). Although a negative study, when data through Week 48 were also considered, the estimated change in 6MWD at Week 24 was 25.5 ± 8.8 m for rituximab and 0.4 ± 7.4 m for placebo (P = 0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of RF (rheumatoid factor), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (receiver operating characteristic area under the curve, 0.88–0.95). Conclusions: B-cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab responsiveness. Clinical trial registered with www.clinicaltrails.gov (NCT 01086540).

Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is subacute cutaneous lupus erythematosus (SCLE) in which the disease onset is associated with the ingestion of an offending medication. It is estimated that approximately one-third of all SCLE cases are drug-induced.1 Idiopathic SCLE and DI-SCLE are serologically, histopathologically, and clinically identical, with both characterized by widespread erythematous annular-polycyclic or papulosquamous psoriasiform lesions.2 DI-SCLE symptoms can arise weeks to years after exposure to a number of medications, including proton-pump inhibitors (PPIs), antihypertensives, antibiotics, and anticonvulsants. A lesser-known phenomenon is a lupus-associated flare or change in lupus phenotype associated with medication initiation in a person who has already been diagnosed with systemic lupus erythematosus (SLE). Cases of patients with previous diagnoses of idiopathic SCLE in remission being exacerbated by PPIs and patients with autoimmune connective tissue diseases developing DI-SCLE after PPI use have been reported.3,4 Here, we present the cases of 3 patients with previous diagnoses of SLE without SCLE skin manifestations developing DI-SCLE after using PPIs or antihypertensives. This pattern has rarely been described in the literature to date and suggests a phenomenon of which clinicians should be aware.

Background Loneliness and social isolation are emerging public health challenges for aging populations. Methods We followed N = 11 302 U.S. Health and Retirement Study participants aged 50–95 from 2006 to 2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018. Results During follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at 2 or more follow-up assessments. For social isolation, these fractions were 21% and 8%. Health and Retirement Study participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen’s d for persistent loneliness and social isolation = 0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk. Conclusions Deficits in social connectedness prevalent in a national sample of U.S. older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.

Purpose With nearly two-thirds of chronic disease attributed to lifestyle, there is a need for physician assistants (PA) to develop competencies in Lifestyle Medicine (LM). The purpose of this study was to assess PA students' skill competencies in exercise and dietary prescription to guide curriculum implementation efforts. Methods An online survey was administered to PA students at a single institution. Results Overall, 74 (63%) students completed the survey, self-reporting moderate competence (range: 1-6) in conducting a physical exam to approve an exercise program (4.17 ± 1.22), designing a nutritional plan (3.76 ± 1.32), and designing an exercise prescription (3.50 ± 1.32). Only about half of the clinical students felt competent in conducting a physical examination to approve an exercise program (56%), determine maximal heart rate (54%), and design a nutritional plan (58%), and only 25% reported competence in designing an exercise prescription. Additionally, 84% of clinical students reported time spent on LM in their program as "poor" or inadequate, and 100% wanted to learn more. Conclusions PA students reported inadequate competence and knowledge in LM but expressed an unanimous interest in learning more about LM during their educational training.

Background and aims Persons with substance use disorders (SUDs) are at elevated risk of suicide death. We identified novel risk factors and interactions that predict suicide among men and women with SUD using machine learning. Design Case-cohort study. Setting Denmark. Participants The sample was restricted to persons with their first SUD diagnosis during 1995-2015 (n = 13,179). Cases were persons who died by suicide in Denmark during 1995-2015 (n = 2,774) and the comparison subcohort was a 5% random sample of individuals in Denmark drawn on January 1, 1995. Measurements Suicide death was recorded in the Danish Cause of Death Registry. Predictors included social and demographic information, mental and physical health diagnoses, surgeries, medications, and poisonings. Findings Persons among the highest risk for suicide, as identified by the classification trees, were men prescribed antidepressants in the 4 years before suicide and had a poisoning diagnosis in the 4 years before suicide; and women who were 30+ years old and had a poisoning diagnosis 4 years before and 12 months before suicide. Among men with SUD, the random forest identified five variables that were most important in predicting suicide: reaction to severe stress and adjustment disorders, drugs used to treat addictive disorders, age 30+ years, antidepressant use, and poisoning in the 4 prior years. Among women with SUD, the random forest found that the most important predictors of suicide were prior poisonings and reaction to severe stress and adjustment disorders. Individuals in the top 5% of predicted risk accounted for 15% of all suicide deaths among men and 24% of all suicides among women. Conclusions In Denmark, prior poisoning and comorbid psychiatric disorders may be among the most important indicators of suicide risk among persons with substance use disorders, particularly among women.

Home and Community-Based Services (HCBS) Medicaid waivers for Serious Emotional Disturbance (SED) extend Medicaid eligibility to youth who otherwise would be financially ineligible and finance a broad array of highly specialized mental health services specific to the needs of youth with SED. This study examines whether these policies are associated with greater public health insurance coverage among youth with severe mental health diagnoses. It also assesses, among youth with severe mental health diagnoses who have public health coverage, whether waiver policies are associated with reduced reports of unmet mental health treatment need and increased reports of adequate mental health coverage. Analysis uses CMS reported data on state HCBS Medicaid waivers in conjunction with data from the National Survey of Children's Health for the years 2016 through 2018. Multi-level, fixed-effects logistic regression models demonstrate that living in a state with an HCBS Medicaid waiver is associated with significantly increased odds of having public insurance among children with concurrent private health coverage (OR 1.89), reduced odds of unmet mental health needs among youth with public coverage (OR 0.45), but not significantly associated with reported adequacy of mental health insurance coverage.

The coronavirus disease 2019 (COVID-19) pandemic, resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused severe and widespread illness in adults, including pregnant women, while rarely infecting neonates. An incomplete understanding of disease pathogenesis and viral spread has resulted in evolving guidelines to reduce transmission from infected mothers to neonates. Fortunately, the risk of neonatal infection via perinatal/postnatal transmission is low when recommended precautions are followed. However, the psychosocial implications of these practices and racial/ethnic disparities highlighted by this pandemic must also be addressed when caring for mothers and their newborns. This review provides a comprehensive overview of neonatal-perinatal perspectives of COVID-19, ranging from the basic science of infection and recommendations for care of pregnant women and neonates to important psychosocial, ethical, and racial/ethnic topics emerging as a result of both the pandemic and the response of the healthcare community to the care of infected individuals.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

SUMMARY The American Society of Plastic Surgeons, the American Academy of Otolaryngology-Head and Neck Surgery, and the American Academy of Facial Plastic and Reconstructive Surgery commissioned the multidisciplinary Rhinoplasty Performance Measure Development Work Group to identify and draft quality measures for the care of patients undergoing both functional and aesthetic rhinoplasty. One outcome measure and three process measures were identified. The outcome looked at patient satisfaction with rhinoplasty procedures. The process measures look at motivations and expectations of the procedure, airway assessment, and nonnarcotic shared decision-making strategies for pain management. All measures in this report were approved by the American Society of Plastic Surgeons Quality and Performance Measures Work Group and Executive Committee, and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, the American Academy of Facial Plastic and Reconstructive Surgery, The Rhinoplasty Society, and the American Association of Oral and Maxillofacial Surgeons. The Work Group recommends the use of these measures for quality initiatives, Continuing Medical Education, Maintenance of Certification, Qualified Clinical Data Registry reporting, and national quality reporting programs.

PURPOSE To identify components of the patient-centered medical home (PCMH) model of care that are associated with lower spending and utilization among Medicare beneficiaries. METHODS Regression analyses of changes in outcomes for Medicare beneficiaries in practices that engaged in particular PCMH activities compared with beneficiaries in practices that did not. We analyzed claims for 302,719 Medicare fee-for-service beneficiaries linked to PCMH surveys completed by 394 practices in the Centers for Medicare & Medicaid Services’ 8-state Multi-Payer Advanced Primary Care Practice demonstration. RESULTS Six activities were associated with lower spending or utilization. Use of a registry to identify and remind patients due for preventive services was associated with all 4 of our outcome measures: total spending was $69.77 less per beneficiary per month (PBPM) (P = 0.00); acute-care hospital spending was $36.62 less PBPM (P = 0.00); there were 6.78 fewer hospital admissions per 1,000 beneficiaries per quarter (P1KBPQ) (P = 0.003); and 11.05 fewer emergency department (ED) visits P1KBPQ (P = 0.05). Using a patient registry for pre-visit planning and clinician reminders was associated with $29.31 lower total spending PBPM (P = 0.05). Engaging patients with chronic conditions in goal setting and action planning was associated with 4.62 fewer hospital admissions P1KBPQ (P = 0.01) and 11.53 fewer ED visits P1KBPQ (P = 0.00). Monitoring patients during hospital stays was associated with $22.06 lower hospital spending PBPM (P = 0.03). Developing referral protocols with commonly referred-to clinicians was associated with 11.62 fewer ED visits P1KBPQ (P = 0.00). Using quality improvement approaches was associated with 13.47 fewer ED visits P1KBPQ (P =0.00). CONCLUSIONS Practices seeking to deliver more efficient care may benefit from implementing these 6 activities.

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.

ObjectiveThe Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial demonstrated clinical benefit of haematopoietic stem cell transplant (HSCT) compared with cyclophosphamide (CYC). We mapped PBC (peripheral blood cell) samples from the SCOT clinical trial to scleroderma intrinsic subsets and tested the hypothesis that they predict long-term response to HSCT.MethodsWe analysed gene expression from PBCs of SCOT participants to identify differential treatment response. PBC gene expression data were generated from 63 SCOT participants at baseline and follow-up timepoints. Participants who completed treatment protocol were stratified by intrinsic gene expression subsets at baseline, evaluated for event-free survival (EFS) and analysed for differentially expressed genes (DEGs).ResultsParticipants from the fibroproliferative subset on HSCT experienced significant improvement in EFS compared with fibroproliferative participants on CYC (p=0.0091). In contrast, EFS did not significantly differ between CYC and HSCT arms for the participants from the normal-like subset (p=0.77) or the inflammatory subset (p=0.1). At each timepoint, we observed considerably more DEGs in HSCT arm compared with CYC arm with HSCT arm showing significant changes in immune response pathways.ConclusionsParticipants from the fibroproliferative subset showed the most significant long-term benefit from HSCT compared with CYC. This study suggests that intrinsic subset stratification of patients may be used to identify patients with SSc who receive significant benefit from HSCT.

BackgroundSince 1999, the rate of fatal prescription opioid overdoses and of suicides has dramatically increased in the USA. These increases, which have occurred among similar demographic groups, have led to the hypothesis that the opioid epidemic contributed to increases in suicidal behavior, though the underlying association remains poorly defined. We examine the association between nonmedical use of prescription opioids/opioid use disorder and suicidal ideation/attempts.MethodsWe used longitudinal data from a national representative sample of the US adult population, the National Epidemiologic Survey on Alcohol and Related Conditions. Participants (n = 34 653) were interviewed in 2001–2002 (wave 1) and re-interviewed approximately 3 years later (wave 2). A propensity score analysis estimated the association between exposure to prescription opioids at wave 1 and prevalent/incident suicidal behavior at wave 2.ResultsHeavy/frequent (⩾2–3 times a month) prescription opioid use was associated with prevalent suicide attempts [adjusted risk ratio (ARR) = 2.75, 95% CI 1.35–5.60]. Prescription opioid use disorder was associated with prevalent (ARR = 1.98, 95% CI 1.20–3.28) and incident suicidal ideation (ARR = 2.59, 95% CI 1.25–5.37), and prevalent attempts (ARR = 4.19, 95% CI 1.71–10.27). None of the exposures was associated with incident suicide attempts.ConclusionsHeavy/frequent opioid use and related disorder were associated with prevalent suicide attempts; opioid use disorder was also associated with the incident and prevalent suicidal ideation. Given population increases in nonmedical use of prescription opioids and disorder, the opioid crisis may have contributed to population increases in suicidal ideation.

Background Transbronchial lung biopsies are commonly performed for a variety of indications. Although generally well tolerated, complications such as bleeding do occur. Description of bleeding severity is crucial both clinically and in research trials; to date, there is no validated scale that is widely accepted for this purpose. Can a simple, reproducible tool for categorizing the severity of bleeding after transbronchial biopsy be created? Methods Using the modified Delphi method, an international group of bronchoscopists sought to create a new scale tailored to assess bleeding severity among patients undergoing flexible bronchoscopy with transbronchial lung biopsies. Cessation criteria were specified a priori and included reaching > 80% consensus among the experts or three rounds, whichever occurred first. Results Thirty-six expert bronchoscopists from eight countries, both in academic and community practice settings, participated in the creation of the scale. After the live meeting, two iterations were made. The second and final scale was vetted by all 36 participants, with a weighted average of 4.47/5; 53% were satisfied, and 47% were very satisfied. The panel reached a consensus and proposes the Nashville Bleeding Scale. Conclusions The use of a simplified airway bleeding scale that can be applied at bedside is an important, necessary tool for categorizing the severity of bleeding. Uniformity in reporting clinically significant airway bleeding during bronchoscopic procedures will improve the quality of the information derived and could lead to standardization of management. In addition to transbronchial biopsies, this scale could also be applied to other bronchoscopic procedures, such as endobronchial biopsy or endobronchial ultrasound-guided needle aspiration.

BACKGROUND The burden of chronic disease in the USA necessitates a shift in medicine and medical education from disease treatment to health and wellness promotion. At the forefront of this shift is the field of lifestyle medicine - the evidence-based use of lifestyle modification to prevent, treat and reverse disease. Health care providers, including physician assistants (PAs), can be the vehicle of behaviour change for patients, families and communities, and must receive adequate training to practice lifestyle medicine. METHODS We describe a pilot lifestyle medicine curriculum implemented through a PA training programme run in the USA in the academic year 2016/2017. The curriculum included four taught modules on lifestyle medicine, two assessment activities and a survey of self-perceived competency, measured before and after the programme. RESULTS Forty students participated in the curriculum. Results showed a significant increase in self-perceived competencies in seven of nine lifestyle medicine areas (p

Importance Prenatal cannabis use continues to increase, yet studies of the demographic, psychiatric, and medical characteristics associated with cannabis use in pregnancy are limited by size and use of self-report, and often do not consider cannabis use disorder (CUD) or concomitant substance use disorders (SUDs). Understanding the factors associated with CUD in pregnancy is paramount for designing targeted interventions. Objective To examine the prevalence of co-occurring psychiatric and medical conditions of US pregnant individuals hospitalized with and without CUD by concomitant SUDs. Design, setting, and participants The study analyzed restricted hospital discharge data from the 2010 to 2018 Healthcare Cost and Utilization Project State Inpatient Databases in 35 states. Data were analyzed from January to August 2021. Weighted linear regressions tested whether the prevalence of psychiatric and medical conditions differed between individuals with and without a CUD diagnosis at hospitalization. Inpatient hospitalizations of pregnant patients aged 15 to 44 years with a CUD diagnosis were identified. Pregnant patients aged 15 to 44 years without a CUD diagnosis were identified for comparison. Patients were further stratified based on concomitant SUD patterns: (1) other SUDs, including at least 1 controlled substance; (2) other SUDs, excluding controlled substances; and (3) no other SUDs. Exposures CUD in pregnancy. Main outcomes and measures Prevalence of demographic characteristics, psychiatric disorders (eg, depression and anxiety), and medical conditions (eg, epilepsy and vomiting). Results The sample included 20 914 591 hospitalizations of individuals who were pregnant. The mean (SD) age was 28.24 (5.85) years. Of the total number of hospitalizations, 249 084 (1.19%) involved CUD and 20 665 507 (98.81%) did not. The proportion of prenatal hospitalizations involving CUD increased from 0.008 in 2010 to 0.02 in 2018. Analyses showed significant differences in the prevalence of almost every medical and psychiatric outcome examined between hospitalizations with and without CUD diagnoses, regardless of concomitant SUDs. Elevations were seen in depression (0.089; 95% CI, 0.083-0.095), anxiety (0.072; 95% CI, 0.066-0.076), and nausea (0.036; 95% CI, 0.033-0.040]) among individuals with CUD only at hospitalization compared with individuals with no SUDs at hospitalization. Conclusions and relevance Considerable growth was observed in the prevalence of CUD diagnoses among individuals hospitalized prenatally and in the prevalence of depression, anxiety, nausea, and other conditions in individuals with CUD at hospitalization. This study highlights the need for more screening, prevention, and treatment, particularly in populations with co-occurring CUD and psychiatric disorders. Research on the determinants and outcomes associated with CUD during pregnancy is needed to guide clinicians, policy makers, and patients in making informed decisions.

Background IL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade of IL-6R with monoclonal antibody tocilizumab would slow loss of residual β cell function in newly diagnosed type 1 diabetes patients. Methods We conducted a multicenter, randomized, placebo-controlled, double-blind trial with tocilizumab in new-onset type 1 diabetes. Participants were screened within 100 days of diagnosis. Eligible participants were randomized 2:1 to receive 7 monthly doses of tocilizumab or placebo. The primary outcome was the change from screening in the mean AUC of C-peptide collected during the first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6–17 years). Results There was no statistical difference in the primary outcome between tocilizumab and placebo. Immunophenotyping showed reductions in downstream signaling of the IL-6R in T cells but no changes in CD4 memory subsets, Th17 cells, Tregs, or CD4+ T effector cell resistance to Treg suppression. A DC subset decreased during therapy but regressed to baseline once therapy stopped. Tocilizumab was well tolerated. Conclusion Tocilizumab reduced T cell IL-6R signaling but did not modulate CD4+ T cell phenotypes or slow loss of residual β cell function in newly diagnosed individuals with type 1 diabetes. Trial Registration ClinicalTrials.gov NCT02293837. Funding NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Allergy and Infectious Diseases (NIAID) UM1AI109565, UL1TR000004 from NIH/National Center for Research Resources (NCRR) Clinical and Translational Science Award (CTSA), NIH/NIDDK P30DK036836, NIH/NIDDK U01DK103266, NIH/NIDDK U01DK103266, 1UL1TR000064 from NIH/NCRR CTSA, NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR001878, UL1TR002537 from NIH/CTSA; National Health and Medical Research Council Practitioner Fellowship (APP1136735), NIH/NIDDK U01-DK085476, NIH/CTSA UL1-TR002494, Indiana Clinical and Translational Science Institute Award UL1TR002529, Vanderbilt Institute for Clinical and Translational Research UL1TR000445. NIH/NCATS UL1TR003142, NIH/CTSA program UL1-TR002494, Veteran Affairs Administration, and 1R01AI132774.

Suicide is a major public health concern in the United States. Between 2000 and 2018, US suicide rates increased by 35%, contributing to the stagnation and subsequent decrease in US life expectancy. During 2019, suicide declined modestly, mostly owing to slight reductions in suicides among Whites. Suicide rates, however, continued to increase or remained stable among all other racial/ethnic groups, and little is known about recent suicide trends among other vulnerable groups. This article (a) summarizes US suicide mortality trends over the twentieth and early twenty-first centuries, (b) reviews potential group-level causes of increased suicide risk among subpopulations characterized by markers of vulnerability to suicide, and (c) advocates for combining recent advances in population-based suicide prevention with a socially conscious perspective that captures the social, economic, and political contexts in which suicide risk unfolds over the life course of vulnerable individuals. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Importance Childhood adversity (CA) is a powerful determinant of long-term physical and mental health that is associated with elevated risk for chronic disease and psychopathology. However, the degree to which CA contributes to mortality as a preventable driver of ill-health and death is unknown. Objective To estimate the contribution of CA to health behaviors, including smoking and sedentary behavior, as well as the annual mortality attributable to CA in the US through influences on leading causes of death (eg, cardiovascular disease). Evidence Review For this systematic review, the PsycINFO and MEDLINE databases were searched on November 15, 2019. The databases were searched for publications from inception (1806 for PsycINFO, 1946 for MEDLINE) to November 15, 2019. Meta-analyses of the associations between CA and morbidity outcomes were included. The population attributable fraction (PAF) was calculated from these associations along with the estimated US prevalence of CA. The PAF was then applied to the number of annual deaths associated with each cause of death to estimate the number of deaths that are attributable to CA. Additionally, the PAF was applied to the incidence of health behaviors to derive the number of cases attributable to CA. Exposure to 1 or more experiences of adversity before the age of 18 years was analyzed, including abuse, neglect, family violence, and economic adversity. Findings A total of 19 meta-analyses with 20 654 832 participants were reviewed. Childhood adversity accounted for approximately 439 072 deaths annually in the US, or 15% of the total US mortality in 2019 (2 854 838 deaths), through associations with leading causes of death (including heart disease, cancer, and suicide). In addition, CA was associated with millions of cases of unhealthy behaviors and disease markers, including more than 22 million cases of sexually transmitted infections, 21 million cases of illicit drug use, 19 million cases of elevated inflammation, and more than 10 million cases each of smoking and physical inactivity. The greatest proportion of outcomes attributable to CA were for suicide attempts and sexually transmitted infections, for which adversity accounted for up to 38% and 33%, respectively. Conclusions and Relevance The results of this systematic review suggest that CA is a leading contributor to morbidity and mortality in the US and may be considered a preventable determinant of mortality. The prevention of CA and the intervention on pathways that link these experiences to elevated disease risk should be considered a critical public health priority.

Background Accurate identification of persons at risk of suicide is challenging because suicide is a rare outcome with a multifactorial origin. The purpose of this study was to predict suicide among persons with depression using machine learning methods. Methods A case-cohort study was conducted in Denmark between January 1, 1995 and December 31, 2015. Cases were all persons who died by suicide and had an incident depression diagnosis in Denmark (n = 2,774). The comparison subcohort was a 5% random sample of all individuals in Denmark at baseline, restricted to persons with an incident depression diagnosis during the study period (n = 11,963). Classification trees and random forests were used to predict suicide. Results In men with depression, there was a high risk of suicide among those who were prescribed other analgesics and antipyretics (i.e., non-opioid analgesics such as acetaminophen), prescribed hypnotics and sedatives, and diagnosed with a poisoning (n = 96; risk = 81%). In women with depression, there was an elevated risk of suicide among those who were prescribed other analgesics and antipyretics, anxiolytics, and hypnotics and sedatives, but were not diagnosed with poisoning nor cerebrovascular diseases (n = 338; risk = 58%). Discussion Psychiatric disorders and their associated medications were strongly indicative of suicide risk. Notably, anti-inflammatory medications (e.g., acetaminophen) prescriptions, which are used to treat chronic pain and illnesses, were associated with suicide risk in persons with depression. Machine learning may advance our ability to predict suicide deaths.

Highlights • Increasing trends in digital media use and suicidal behavior were observed. • Modest proportions of these trends were directly associated with one another. • Mediation analyses can be used to assess the association between different time trends., U.S. adolescent suicidal behavior and digital media use prevalence have contemporaneously increased this decade in population-level ecological analyses. The purpose of this study was to determine whether these two trends are directly associated by using multi-year person-level data to test whether the association of year with suicidal behavior was mediated by digital media use. Data were from the Youth Risk Behavior Surveillance System (2009–2017), a nationally-representative biennial cross-sectional self-report survey of U.S. students (N = 72,942). Mediation analysis was used to estimate the proportion of cross-year changes in suicidal behavior that were mediated by concurrent changes in leisure-time digital media use. Past-year suicidal behavior in 2011 (19.6%), 2013 (20.4%), 2015 (21.7%), and 2017 (20.5%) increased relative to 2009 (17.1%). Hours of daily digital media use in 2011 (mean[SD] = 2.65[1.86]), 2013 (mean[SD] = 3.02[2.08]), 2015 (mean[SD] = 2.97[2.12]), and 2017 (mean[SD] = 3.01[2.18) increased vs. 2009 (mean[SD] = 2.31[1.81]). The association of survey year with suicidal behavior was mediated by digital media use—20.5%(95%CI = 16.2, 24.8), 34.3%(95%CI = 24.5, 44.1), 22.8%(95%CI = 17.3, 28.0), and 41.4%(95%CI = 33.9, 49.5) of cross-year suicidal behavior prevalence increases (vs. 2009) for 2011, 2013, 2015, and 2017, respectively, were mediated by concurrent digital media use increases. Therefore, small proportions of the 2009–2017 increases in U.S. adolescent suicidal behavior are associated with concurrent increasing digital media use trends. Further exploration of these trends is warranted.

Over the past century, the field of epidemiology has evolved and adapted to changing public health needs. Challenges include newly emerging public health concerns across broad and diverse content areas, new methods, and vast data sources. We recognize the need to engage and educate the next generation of epidemiologists and prepare them to tackle these issues of the 21st century. In this commentary, we suggest a skeleton framework upon which departments of epidemiology should build their curriculum. We propose domains that include applied epidemiology, biological and social determinants of health, communication, creativity and ability to collaborate and lead, statistical methods, and study design. We believe all students should gain skills across these domains to tackle the challenges posed to us. The aim is to train smart thinkers, not technicians, to embrace challenges and move the expanding field of epidemiology forward.

Prescription drug monitoring programs (PDMPs) are a crucial component of federal and state governments’ response to the opioid epidemic. Evidence about the effectiveness of PDMPs in reducing prescription opioid–related adverse outcomes is mixed. We conducted a systematic review to examine whether PDMP implementation within the United States is associated with changes in 4 prescription opioid–related outcome domains: opioid prescribing behaviors, opioid diversion and supply, opioid-related morbidity and substance-use disorders, and opioid-related deaths. We searched for eligible publications in Embase, Google Scholar, MEDLINE, and Web of Science. A total of 29 studies, published between 2009 and 2019, met the inclusion criteria. Of the 16 studies examining PDMPs and prescribing behaviors, 11 found that implementing PDMPs reduced prescribing behaviors. All 3 studies on opioid diversion and supply reported reductions in the examined outcomes. In the opioid-related morbidity and substance-use disorders domain, 7 of 8 studies found associations with prescription opioid–related outcomes. Four of 8 studies in the opioid-related deaths domain reported reduced mortality rates. Despite the mixed findings, emerging evidence supports that the implementation of state PDMPs reduces opioid prescriptions, opioid diversion and supply, and opioid-related morbidity and substance-use disorder outcomes. When PDMP characteristics were examined, mandatory access provisions were associated with reductions in prescribing behaviors, diversion outcomes, hospital admissions, substance-use disorders, and mortality rates. Inconsistencies in the evidence base across outcome domains are due to analytical approaches across studies and, to some extent, heterogeneities in PDMP policies implemented across states and over time.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

Purpose The purpose of this paper is to address the barrier to care experienced by LGBTQIA+ populations by binary language for gender, sexual orientation and relationship status. Design/methodology/approach The authors review the research that shows linguistic barriers are a significant obstacle to healthcare for LGBTQIA+ communities. The authors describe both a process and revisions for addressing language bias in psychiatric intake/research research materials as well as quantify its impact in an adult psychotherapy clinic in a public hospital. Findings Patients self-identified their gender, sexual orientation and relationship status in a variety of ways when not presented with binaries and/or pre-established response choices. In addition, the non-response rate to questions decreased and the authors received positive qualitative feedback. The authors also present the revisions to the intake/research materials. Practical implications Other healthcare settings/clinicians can revise language in order to remove significant barriers to treatment and in doing so, be welcoming, non-pathologizing and empowering for LGBTQIA+ consumers of mental health services (as well as for non-LGBTQIA+ consumers who are in non-traditional relationships). Social implications This work is one step in improving healthcare and the healthcare experience for LGBTQIA+ communities and for those in non-traditional relationships. Originality/value This work is set in a public safety-net hospital providing care for underserved and diverse populations. This paper describes the process of revising psychiatric materials to be more inclusive of the range of self-identity are: gender, sexual orientation and relationship status.

Objectives 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. Methods We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti–CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. Results Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. Conclusion This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.

Background/aim:Cost-efficient methods are essential for successful participant recruitment in clinical trials. Patient portal messages are an emerging means of recruiting potentially eligible patients into trials. We assessed the response rate and complaint rate from direct-to-patient, targeted recruitment through patient portals of an electronic medical record for a clinical trial, and compared response rates by differences in message content.Methods:The Study to Understand Fall Reduction and Vitamin D in You (STURDY) trial is a National Institutes of Health–sponsored, community-based study of vitamin D supplementation for fall prevention in older adults conducted at Johns Hopkins. Potential participants were identified using the Epic electronic medical record at the Johns Hopkins Health System based on age (≥70 years), ZIP code (30-mile radius of study site), and prior activation of a patient portal account. We prepared a shorter message and a longer message. Both had basic information about study participation, but the longer message also contained information about the significance of the study and a personal invitation from the STURDY principal investigator. The Hopkins Institutional Review Board did not require prior consent from the patient or their providers. We calculated the response rate and tracked the number of complaints and requests for removal from future messages. We also determined response rate according to message content.Results:Of the 5.5 million individuals receiving care at the Johns Hopkins Health System, a sample of 6896 met our inclusion criteria and were sent one patient portal recruitment message between 6 April 2017 and 3 August 2017. Assessment of enrollment by this method ended on 1 December 2017. There were 116 patients who expressed interest in the study (response rate: 1.7%). Twelve (0.2%) recipients were randomized. There were two complaints (0.03%) and one request to unsubscribe from future recruitment messages (0.01%). Response rate was higher with the longer message than the shorter message (2.1% vs 1.2%; p = 0.005).Conclusion:Patient portal messages inviting seniors to participate in a randomized controlled trial resulted in a response rate similar to commercial email marketing and resulted in very few complaints or opt-out requests. Furthermore, a longer message with more content enhanced response rate. Recruitment through patient portals might be an effective strategy to enroll trial participants.

PURPOSE: To estimate the population-based incidence of HPV vaccination after childhood cancer. METHODS: Pediatric and young adult cancer survivors identified in the institutional Comprehensive Cancer Center registry were linked to the North Carolina Immunization Registry (NCIR). Initiation and completion of any HPV vaccine was evaluated in survivors born between 1984 and 2002 with an NCIR record by December 2014. Descriptive statistics and Kaplan-Meier estimates of cumulative incidence were stratified by sex and age at eligibility for vaccine. Cox proportional hazards were conducted and stratified by sex. RESULTS: Among 879 (n = 428 female; n = 451 male) study-eligible cancer survivors without prior HPV vaccination (n = 501 < 18 years, n = 378 ≥ 18 years at the time of eligibility), the cumulative incidence of HPV vaccine initiation following cancer therapy was 48.1% among females at 8.2 years and 29.2% among males at 5.0 years after vaccine eligibility among those < 18 years, and 6.2% among females at 8.1 years and 2.0% among males at 4.2 years after vaccine eligibility among those ≥ 18 years. Among those who initiated vaccination, 53% of females and 43% of males completed a 3-dose series. Younger age at cancer diagnosis (≤ 10 and 11–14 years vs. ≥ 15 years) and shorter interval from diagnosis to vaccine eligibility were more likely to initiate vaccination in models adjusted for age at eligibility, race/ethnicity, cancer type, relapse, and transplant. CONCLUSIONS: Despite the benefit of a cancer prevention strategy, cancer survivors are sub-optimally vaccinated against HPV. IMPLICATIONS FOR CANCER SURVIVORS: Immunization registries can help oncologists and primary care providers identify gaps in vaccination and target HPV vaccine delivery in survivors.

OBJECTIVES: To examine generational differences in longitudinal blood pressure trajectories by region following socioeconomic transitions, which is important for establishing the population risk of cardiovascular diseases (CVDs). METHODS: With data from the China Health and Nutrition Survey (1991–2011), we used multilevel growth-curve models to estimate systolic/diastolic blood pressure (SBP/DBP) levels at the mean age and rates of change by cohort (born between 1931 and 1980), region, and sex. RESULTS: Younger cohorts generally had higher SBP/DBP levels at 44.5 years but lower growth rates in SBP/DBP than older cohorts. They became prehypertensive (SBP ≥ 120 mm Hg or DBP ≥ 80 mm Hg) at an earlier age. The upward shift of SBP/DBP trajectories across cohorts was more pronounced in the Coastal and Southern Mountainous Regions than the Northeastern and Inland Regions, and for males versus females. CONCLUSIONS: Younger cohorts have a longer lifetime duration of being susceptible to CVDs, posing warnings for an increased burden of CVDs. Generational differences in BP trajectories and geographic and sex variations in the cohort trends highlight the need for tailored interventions to tackle the generation, region, and sex-based risk of CVDs.

Background Mood and anxiety disorders are associated with growing burden of disease. Recent evidence shows that monitoring and enhancing positive mental health might be one direction to reduce this burden. The aim was to determine whether positive mental health predict recovery from mental disorders. Methods The study population consisted of 414 participants with a 12-month disorder from the representative general population Netherlands Mental Health Survey and Incidence Study-2. Independent positive mental health indicators were mental well-being, its subscales emotional, social and psychological well-being and the category flourishing mental health. Recovery was defined as no longer fulfilling DSM-IV criteria of the index disorder 3 years later. Results Despite meeting the criteria of a 12-month mental disorder, 19% with anxiety disorder were flourishing and 14% with mood disorder. Logistic regression analyses controlled for sociodemographics, physical health, life-events, service use, psychotropic medication, comorbidity and clinical severity showed that positive mental health positively influenced recovery from anxiety disorder (mainly by emotional and psychological well-being) and did not influence recovery from mood disorder. Limitations The results are not generalizable to psychiatric patients in treatment settings and might differ for specific disorders within each DSM-IV category. Conclusions Clinicians are encouraged to measure positive mental health in their patients and to improve positive mental health particularly in people with an anxiety disorder. The non-significant relation between positive mental health and recovery from mood disorder warrants further research, for example through using more in-depth assessment of positive mental health components and by investigating recovery from less severe mood disorders.

Background Ethiopia has been expanding maternity waiting homes to bridge geographical gaps between health facilities and communities in order to improve access to skilled care. In 2015, the Ministry of Health revised its national guidelines to standardize the rapid expansion of waiting homes. Little has been done to document their distribution, service availability and readiness. This paper addresses these gaps as well as their association with perinatal mortality and obstetric complication rates. Methods We utilized data from the 2016 national Emergency Obstetric and Newborn Care assessment, a census of 3804 public and private health facilities. Data were collected between May and December 2016 through interviews with health care workers, record reviews, and observation of infrastructure. Descriptive statistics describe the distribution and characteristics of waiting homes and linear regression models examined the correlation between independent variables and institutional perinatal and peripartum outcomes. Results Nationally, about half of facilities had a waiting home. More than two-thirds of facilities in Amhara and half of the facilities in SNNP and Oromia had a home while the region of Gambella had none. Highly urbanized regions had few homes. Conditions were better among homes at hospitals than at health centers. Finished floors, electricity, water, toilets, and beds with mattresses were available at three (or more) out of four hospital homes. Waiting homes in pastoralist regions were often at a disadvantage. Health facilities with waiting homes had similar or lower rates of perinatal death and direct obstetric complication rates than facilities without a home. The perinatal mortality was 47% lower in hospitals with a home than those without. Similarly, the direct obstetric complication rate was 49% lower at hospitals with a home compared to hospitals without. Conclusions The findings should inform regional maternal and newborn improvement strategies, indicating gaps in the distribution and conditions, especially in the pastoralist regions. The impact of waiting homes on maternal and perinatal outcomes appear promising and as homes continue to expand, so should efforts to regularly monitor, refine and document their impact.

ObjectivesTo estimate associations between psychiatric disorders and gun carrying among adolescents and to estimate the total number of adolescents in the US who have psychiatric disorders and report carrying guns.Study designWe used cross-sectional data from the National Comorbidity Survey - Adolescent Supplement, a nationally representative sample of adolescents age 13-18years (N=10 123; response rate=75.6%). Psychiatric disorders were assessed using the Composite International Diagnostic Interview. Gun carrying in the 30days prior to the interview was assessed by self-report. We used multivariable Poisson regression to test for associations.ResultsThe analytic sample included 10 112 adolescents, 2.4% of whom reported carrying a gun in the prior 30days. The prevalence of gun carrying was greater among adolescents with conduct disorder (adjusted prevalence ratio [APR]=1.88, 95% CI 1.38, 2.57), drug use disorders (APR=1.91, 95% CI 1.05, 3.45), and specific phobias (APR=1.54, 95% CI 1.07, 2.22) compared with adolescents without these disorders. We estimated that 1.1% (95% CI 0.77, 1.48) of adolescents with a disorder associated with self- or other-directed violence also carry guns. Nationally, that is approximately 272 000 adolescents with both risk factors.ConclusionsSpecific psychiatric disorders are associated with an increased risk of gun carrying among adolescents, but the vast majority of adolescents with psychiatric disorders did not report gun carrying. Targeted efforts to assess access to and use of firearms in mental healthcare and other clinical settings are important, as are efforts to identify population approaches to prevention.

Background: Lack of established criteria for sunscreen product recommendations and potentially allergenic ingredients in sunscreens pose an issue for physicians and patients with autoimmune skin conditions. Objective: We reviewed popular sunscreens for effectiveness and potential allergenicity for recommendation and use in the autoimmune skin condition population. Methods: In this cohort study, we selected sunscreens from the bestseller lists of Amazon, Target, and CVS. Of those, sunscreens with sun protection factor of 50 to 99 and 100 that met our effectiveness criteria (52 sunscreens) were analyzed for allergenic ingredients. An allergen list was developed from the North American Contact Dermatitis Group core data and stratified into low-prevalence and high-prevalence allergens. Results: The allergenicity of popular sunscreens that met our effectiveness criteria are organized in a table by number of tiered potential allergens. Although no sunscreen was allergen-free, several products contained a minimal number of low-prevalence allergens. The most common low-prevalence allergens were chemical sunscreen ingredients avobenzone, octocrylene, and oxybenzone, and the most common high-prevalence allergen was fragrance. A limitation is that not all U.S. sunscreens were analyzed. Conclusion: With the wide range of sunscreens available, physicians and patients should be aware of the effectiveness and potential allergenicity of sunscreens and make recommendations and consumption choices accordingly. Keywords: dermatology, sunscreen, photosensitivity, allergens, contact dermatitis, autoimmune skin