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Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10−11), rs12454712 (BCL2; P = 2.7 × 10−8), and rs10506418 (FAM19A2; P = 1.9 × 10−8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.

Indications for reverse total shoulder arthroplasty (RTSA) have expanded to include primary glenohumeral osteoarthritis (GHOA) with an intact rotator cuff. Limited evidence exists on RTSA in patients with primary GHOA and no posterior glenoid wear (Walch A1, A2, and B1 morphologies). The purpose of this retrospective cohort study was to determine if glenoid morphology is associated with clinical outcomes in patients undergoing RTSA for primary GHOA.A retrospective review of prospectively collected data was performed in patients undergoing primary RTSA for GHOA with a minimum of 2-year clinical follow-up. Preoperative computed tomography and magnetic resonance imaging were used to categorize glenoid morphology as described by the modified Walch classification. Pre- and postoperative American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Single Assessment Numeric Evaluation (SANE), visual analog scale (VAS) pain scores, and range of motion (ROM) measurements were compared across Walch glenoid subtypes. The percentage of patients that reached previously established clinically significant thresholds for minimal clinically important difference (MCID) and substantial clinical benefit (SCB) was also comparatively assessed. Multivariable analysis was used to evaluate the association between glenoid morphology and postoperative ASES score while controlling for potentially confounding variables.Of the 247 consecutive patients, 197 were available at a minimum 2-year follow-up (80%). Significant improvements were seen in ASES, VAS pain, SANE, and ROM from baseline to final postoperative follow-up in the combined patient cohort (all P.001). Most (98.0%) patients reached MCID, and 90.9% of patients reached SCB for ASES threshold. No significant differences were found among Walch subtypes in terms of preoperative to postoperative improvement in ASES (P = .39), SANE (P = .4), VAS pain (P = .49), forward elevation (P = .77), external rotation (P = .45), or internal rotation (P= 0.1). The only significant difference in postoperative outcomes between Walch glenoid subtypes was higher postoperative ASES scores among type B3 glenoids compared with type A1 glenoids (P = .03) on univariate analysis. However, no individual Walch glenoid subtype was associated with lower postoperative ASES scores on multivariable analysis (P.05).Primary RTSA provides excellent short-term outcomes in patients with glenohumeral arthritis with intact rotator cuff, regardless of the degree of preoperative glenoid deformity. Surgeons can use these data to support the use of RTSA for glenohumeral arthritis in a more standardized way.

Background People are increasingly turning to online search engines for health information. We analyzed Google search queries to determine the most frequently asked topics and questions related to shoulder arthroplasty and the sources of the websites provided to address these questions. Methods Search terms for shoulder arthroplasty were entered into Google. Machine learning–based natural language processing algorithms within Google were used to mine search logs to identify frequently asked questions about shoulder arthroplasty. These questions with their associated websites were extracted and categorized by two independent reviewers. Results A total of 300 questions were extracted with 156 associated websites. The most popular question topics were related to the timeline of recovery (16.3%), ability to perform specific activities (15.7%), technical details of surgery (14.3%), and activity restrictions (12%). Frequently asked questions had to do with the fastest means of recovery, duration of physical therapy, sling use, time spent sleeping upright in a recliner, time off work, location of surgical incision, resumption of sports, and the ability to use the bathroom. The most common websites provided to address the questions were academic (25.3%), private practice (23%), and government (20.3%). Conclusion The most frequently asked questions on Google about shoulder arthroplasty centered around postoperative rehabilitation and restrictions, with information originating from variable sources. Our data can be used to counsel patients and set expectations about recovery and serve as a framework for the development of targeted patient education materials. Level of evidence Level VI; Descriptive Study

Though long-neglected, the right heart (RH) is now widely accepted as a pivotal player in heart failure (HF) either with reduced (HFrEF) or preserved (HFpEF) ejection fraction. The chronic overload of the pulmonary microcirculation results in an initial phase characterized by right ventricular (RV) hypertrophy, right atrial (RA) dilation, and diastolic dysfunction. This progresses to overt right heart failure (RHF) when RV dilation and systolic dysfunction lead to RV-pulmonary arterial uncoupling with low RV output. In the context of its established relevance to progression of HF, clinicians should consider assessment of the right heart with information from clinical assessment, biomarkers, and imaging. Notably, no single parameter can predict prognosis alone in HF. Assessments should simultaneously encompass RV systolic function, pulmonary pressures, an estimation of RV-PA coupling, and right heart morphology. Despite a large volume of evidence indicating the relevance of right heart function to the clinical syndrome of HF, evidence-based management strategies are lacking. Targeting RH dysfunction in HF should be an objective of future investigations, being an unmet need in the current management of HF.

Pulmonary arterial hypertension is a rare disease characterized by pulmonary microvasculature remodeling leading to right ventricular failure and death. Medical management of pulmonary hypertension has grown increasingly complex as more therapeutic agents have been developed. Evolving treatment strategies leveraging the endothelin, nitric oxide, and prostacyclin pathways lead to improved exercise capacity and outcomes in patients; however, significant opportunities for advancement remain.

Expanding Donation after circulatory death (DCD) multi-organ recovery to include the heart presents logistical and technical challenges for all teams participating in the process. Strategies to optimally coordinate the activities of multi-organ DCD recovery teams to facilitate expeditious, coordinated multi-organ protection and safe recovery are discussed.

Background Distal humerus fractures (DHF) pose a treatment challenge in elderly patients. We sought to systematically review and report the clinical outcomes of the nonoperative approach (e.g., “bag of bones”) for the treatment of these injuries, and the rate of conversion to delayed surgery. Methods A comprehensive review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted. Studies involving outcomes following nonoperative treatment of DHF in patients >65 years of age were included from 1985 to present. Data regarding patient age, DHF type, nonoperative treatment method, complications, conversion to delayed surgery, range of motion, union rate, and surgeon and patient reported outcome measures were extracted. Results A total of five studies met inclusion criteria (all level IV evidence), yielding a total of 143 patients (mean age: 73.5 years to 87.4 years) with 7.1 months to 55 months of follow-up. The mean Mayo Elbow Performance Index (MEPI) scores were good to excellent across several studies (range 83 - 93.1). Multiple studies reported good range of motion (mean arc of motion: 81 to 106 degrees) and low levels of upper extremity disability (mean Quick Disability of the Arm-Shoulder-Hand (Q-DASH) scores: 31.3 to 38.5) at final follow-up. The rate of conversion to total elbow arthroplasty and operative fixation ranged from 0% to 7.5% and 0% to 5%, respectively. Conclusion Nonoperative management of distal humerus fractures in the elderly seems to be associated with acceptable functional outcomes and low rates of delayed surgery. This information is important for patient counseling and treatment decision-making.

Objectives The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patie...

The presence of functional somatic syndromes (chronic physical symptoms with no identifiable organic cause) in patients undergoing elective joint arthroplasty may affect the recovery experience. We explored the prevalence of functional somatic syndromes among shoulder arthroplasty patients, as well as their association with postoperative outcomes and costs.We identified 480 patients undergoing elective total shoulder arthroplasty (anatomic or reverse) between 2015 and 2018 in our institutional registry with minimum 2-year follow-up. Medical records were queried for the presence of 4 well-recognized functional somatic syndromes: fibromyalgia, irritable bowel syndrome, chronic headaches, and chronic low-back pain. Multivariable linear regression modeling was used to determine the independent association of these diagnoses with hospitalization time-driven activity-based costs and 2-year postoperative American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and pain scores.Nearly 1 in 5 patients (17%) reported at least 1 functional somatic syndrome. These patients were more likely to be women, to be chronic opioid users, to report more allergies, to have a diagnosis of anxiety, and to have shoulder pathology other than degenerative joint disease (all P ≤ .001). After multivariable adjustment, the presence of at least 1 functional somatic syndrome was independently predictive of lower 2-year ASES (-9.75 points) and SANE (-7.63 points) scores and greater residual pain (+1.13 points) (all P ≤ .001). When considered cumulatively, each additional functional disorder was linked to a stepwise decrease in ASES and SANE scores and an increase in residual pain (P.001). These patients also incurred higher hospitalization costs, with a stepwise rise in costs with an increasing number of disorders (P.001).Functional somatic syndromes are common in patients undergoing shoulder arthroplasty and correlate with suboptimal outcomes and greater resource utilization. Efforts to address the biopsychosocial determinants of health that affect the value proposition of shoulder arthroplasty should be prioritized in the redesign of care pathways and bundling initiatives.

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR. hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.

Year-round intensive, single-sport training beginning at an young age is an increasingly common trend in the youth athlete population. Early sport specialisation may be ineffective for long-term athletic success and contribute to an increased risk of physical injury and burn-out. The medical community has noted that repetitive movement patterns may occur in non-diversified activity and this may contribute to overuse injury in young athletes. Studies have begun to identify an association between early sport specialisation and lower extremity injuries in the youth athlete population that is independent of training volume. Recent literature has suggested that sport diversification, not specialisation, is a better path for athletic success and minimised lower extremity injury risk.

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.

Acute pulmonary embolism (PE) is associated with significant morbidity and mortality. The management paradigm for acute PE has evolved in recent years with wider availability of advanced treatment modalities ranging from catheter-directed reperfusion therapies to mechanical circulatory support. This evolution has coincided with the development and implementation of institutional pulmonary embolism response teams (PERT) nationwide and internationally. Because most institutions are not equipped or staffed for advanced PE care, patients often require transfer to centers with more comprehensive resources, including PERT expertise. One of the unmet needs in current PE care is an organized approach to the process of interhospital transfer (IHT) of critically ill PE patients. In this review, we discuss medical optimization and support of patients before and during transfer, transfer checklists, defined roles of emergency medical services, and the roles and responsibilities of referring and receiving centers involved in the IHT of acute PE patients.

Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.

Introduction In the event-driven GRIPHON randomised-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag. Methods Patients randomised to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3 days and 30 days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019. Results Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7 months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomised to selexipag in GRIPHON. Kaplan–Meier survival estimates (95%CI) at 1, 3, 5 and 7 years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively. Conclusions These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen. Trial Registration ClinicalTrials.gov Identifiers: NCT01106014 and NCT01112306 Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01898-1.

Delirium is a debilitating medical condition that disproportionately affects hospitalized older adults(1) and is associated with adverse health outcomes, increased mortality, and high medical costs.(2) Efforts to understand delirium risk in hospitalized older adults have focused on examining medical comorbidities, pre-existing cognitive deficits, and other clinical and demographic factors present in the period proximate to the hospitalization.(3,4) The contribution of social determinants of health (SDOH), including social circumstances, environmental characteristics, and early-life exposures, referred as the social exposome,(5) to delirium risk are poorly understood. Increased knowledge about the influence of SDOH will offer a more comprehensive understanding of factors that may increase vulnerability to delirium and poor outcomes. Clinically, these efforts can guide the development and implementation of holistic preventive strategies to improve clinical outcomes. We propose a social determinants of health (SDOH) framework for delirium tailored to older adults. We provide the definition, description, and rationale for the domains and variables in our proposed model.

Background: Bradykinesia is the defining motor feature of Parkinson’s disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. Objective: To develop a quantitative method to track repetitive tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia. Methods: This was a cross-sectional study of 99 participants (early-stage PD = 26, controls = 64, idiopathic anosmia = 9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per second. From each video, amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second) was extracted. Clinical assessment was based on the motor section of the MDS-UPDRS. Results: People in the early stage of PD performed the task with slower velocity (p

Background and ObjectivesAndexanet alfa was recently approved as a reversal agent for the factor Xa inhibitors (FXais) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study.MethodsWe simulated potential downstream implications of andexanet alfa across a range of possible hemostatic effects using data from a single center that treats FXai-associated ICH with prothrombin complex concentrate (PCC). We determined baseline probabilities of inadequate hemostasis across patients taking FXai and those not taking FXai via multivariable regression models and then determined the probabilities of unfavorable 3-month outcome (modified Rankin Scale score 4–6) using models comprising established predictors and each patient's calculated probability of inadequate hemostasis. We applied bootstrapping with model parameters from this derivation cohort to simulate a range of hemostatic improvements and corresponding outcomes and then calculated absolute risk reduction (relative to PCC) and projected number needed to treat (NNT) to prevent 1 unfavorable outcome.ResultsTraining models using real-world patients (n = 603 total, 55 on FXai) had good accuracy in predicting inadequate hemostasis (area under the curve [AUC] 0.78) and unfavorable outcome (AUC 0.78). Inadequate hemostasis was strongly associated with unfavorable outcome (odds ratio 4.5, 95% confidence interval [CI] 2.0–9.9) and occurred in 11.4% of patients taking FXai. Across simulated patients taking FXai comparable to those in A Study in Participants With Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4) study, predicted absolute risk reduction of unfavorable outcome was 4.9% (95% CI 1.3%–7.8%) when the probability of inadequate hemostasis was reduced by 33% and 7.4% (95% CI 2.0%–11.9%) at 50% reduction, translating to projected NNT of 21 (cumulative cost $519,750) and 14 ($346,500), respectively.DiscussionEven optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered. Placebo-controlled randomized trials are needed before its use can definitively be recommended.

Objective To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. Subjects and Methods A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. Results The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. Conclusions The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

INTRODUCTION Pseudoaneurysms are uncommon but potentially life-threatening. Treatment may involve a variety of interventions including observation, manual compression, ultrasound-guided thrombin injection and a variety of endovascular and surgical techniques. Current treatments are largely based on observational data and there is no consensus on management. This study aimed to provide evidence for guiding clinical decisions regarding visceral artery pseudoaneurysm and peripheral artery pseudoaneurysm management. METHODS Retrospective single-centre review of patients diagnosed with visceral and peripheral artery pseudoaneurysms at a tertiary hospital (2010-2020). RESULTS There were 285 patients included in this study. A total of 86 patients were diagnosed with a visceral artery pseudoaneurysm, and 49 of these (57%) were caused by trauma. A total of 199 patients were identified with a peripheral pseudoaneurysm; 76 of these (38%) were caused by trauma and 69 (35%) were due to access site complication during an endovascular procedure. Initial technical success was achieved in 266 patients (93.3%) with 19 requiring an additional treatment to achieve success. Conservative treatment (100% success), endovascular treatment (98.1%) and surgery (100%) were more successful than ultrasound-guided compression (63.6%) and thrombin injection (83.8%). The median time from diagnosis to intervention was

Objective To report a unique case and literature review of post COVID-19 vaccination associated transverse myelitis and with abnormal MRI findings. Background Coronavirus disease have been reported to be associated with several neurological manifestations such as stroke, Guillain-Barré syndrome, meningoencephalitis amongst others. There are only a few reported cases of transverse myelitis with the novel coronavirus (n-CoV-2). Here, we identify a post COVID-19 vaccination patient diagnosed with acute transverse myelitis. Method A retrospective chart review of a patient diagnosed with post SARS-CoV-2 vaccination acute transverse myelitis, and a review of literature of all the reported cases of other post vaccination and transverse myelitis, from December 1st, 2010 till July 15th, 2021, was performed. Conclusion To our knowledge, this is the one of early reported case of transverse myelitis and with post SARS-CoV-2 vaccination, who responded well to plasmapheresis. Further studies would be recommended to identify the underlying correlation between COVID-19 vaccination and transverse myelitis.

Purpose The purpose of this study was to determine the cost-effectiveness of the most commonly used type of antimicrobial silver-impregnated occlusive dressing (Aquacel Ag, ConvaTec, Oklahoma City, OK, USA) for prosthetic shoulder infection (PSI) prevention after shoulder arthroplasty. Methods Data regarding the cost of silver-impregnated occlusive dressing, cost to treat a PSI and initial infection rates after shoulder arthroplasty were calculated from available literature. Using a break-even economic analysis, we developed an equation that incorporated these variables to determine the absolute risk reduction (ARR) in infection rate required to make the use of this dressing cost-effective. To provide a widely applicable and reusable model, multiple simulations were performed at varying unit costs, infection rates, and PSI-related care costs. Results At a dressing cost of $34.00 and presuming a cost of $50,230 for treating a PSI, these dressings are considered cost-effective if their use prevents at least 1 infection in 1471 TSA (ARR of 0.068% from the initial infection rate of 0.7%). The cost-effectiveness of this dressing was maintained through a realistic range of dressing and PSI treatment costs, while initial infection rate was found not to influence cost-effectiveness. Conclusions Antimicrobial silver-impregnated occlusive dressings represent a cost-effective infection prevention strategy after shoulder arthroplasty. The presented model serves as a useful resource to aid in weighing the economic effects of implementing any potential prophylactic measures aimed at minimizing infections after shoulder arthroplasty. Level of Evidence Level IV; Economic Decision Analysis

There are conflicting data regarding the benefit of compression-only bystander cardiopulmonary resuscitation (CO-CPR) compared with CPR with rescue breathing (RB-CPR) after pediatric out-of-hospital cardiac arrest (OHCA).This study sought to test the hypothesis that RB-CPR is associated with improved neurologically favorable survival compared with CO-CPR following pediatric OHCA, and to characterize age-stratified outcomes with CPR type compared with no bystander CPR (NO-CPR).Analysis of the CARES registry (Cardiac Arrest Registry to Enhance Survival) for nontraumatic pediatric OHCAs (patients aged ≤18 years) from 2013-2019 was performed. Age groups included infants (1 year), children (1 to 11 years), and adolescents (≥12 years). The primary outcome was neurologically favorable survival at hospital discharge.Of 13,060 pediatric OHCAs, 46.5% received bystander CPR. CO-CPR was the most common bystander CPR type. In the overall cohort, neurologically favorable survival was associated with RB-CPR (adjusted OR: 2.16; 95% CI: 1.78-2.62) and CO-CPR (adjusted OR: 1.61; 95% CI: 1.34-1.94) compared with NO-CPR. RB-CPR was associated with a higher odds of neurologically favorable survival compared with CO-CPR (adjusted OR: 1.36; 95% CI: 1.10-1.68). In age-stratified analysis, RB-CPR was associated with better neurologically favorable survival versus NO-CPR in all age groups. CO-CPR was associated with better neurologically favorable survival compared with NO-CPR in children and adolescents, but not in infants.CO-CPR was the most common type of bystander CPR in pediatric OHCA. RB-CPR was associated with better outcomes compared with CO-CPR. These results support present guidelines for RB-CPR as the preferred CPR modality for pediatric OHCA.

When infants are identified with a difference of sex development (DSD), a thoughtful approach to imaging is essential to appropriate clinical management. This review provides a comprehensive guide for radiologists who are tasked with performing this critical assignment. We review the embryologic basis of DSDs, with attention to the imaging findings that can indicate specific diagnoses. We also discuss techniques for optimal imaging, including strategies for identifying the gonads by US, tactics for performing genitograms with fluoroscopy and contrast-enhanced US, and the appropriate utilization of MRI. Finally, we review the clinical data and imaging findings that characterize some of the most common DSDs, including congenital adrenal hyperplasia, complete androgen insensitivity syndrome and gonadal dysgenesis.

Purpose To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. Materials and methods We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring 24 h after presentation (“later-onset”). Results Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5–7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1–8.2]), and troponin (OR 3.0 [95% CI 1.2–7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. Conclusions Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.

Background We used online crowdsourcing to explore public perceptions and attitudes towards virtual orthopaedic care, and to identify factors associated with perceived difficulty navigating telehealth services during the COVID-19 pandemic. Methods A modified version of the validated Telemedicine Satisfaction and Usefulness Questionnaire was completed by 816 individuals using crowd-sourcing methods. Multivariable logistic regression modelling was used to determine population characteristics associated with perceived difficulty using telehealth technology. Results Most respondents (85%) believed that telehealth visits would be a convenient form of healthcare delivery, and 64% would prefer them over in-person office visits. The majority (92%) agreed that telehealth would save them time, but 81% had concerns regarding the lack of physical contact during a musculoskeletal examination. More respondents would feel comfortable using telehealth for routine follow-up care (81%) compared to initial assessment visits (59%) and first postoperative appointments (60%). Roughly 1 in 15 (7%) expressed difficulty with using telehealth; these respondents were more often unmarried, lower-income, and more medically infirm, and reported greater symptoms of depression. After multivariable adjustment, lower income and poor health were retained as predictors of difficulty with navigating telehealth technology (p = 0.027,p = 0.036, respectively). Conclusion The majority of the public appears receptive to telehealth for orthopaedic care for both new patient visits and follow-up appointments. The finding that people with multiple chronic conditions and psychosocial needs struggle to engage with telehealth suggests that those who arguably stand to benefit the most from continued care are the ones being unintentionally left out of this digitization boom.

Herpes Zoster Ophthalmicus (HZO) is a rare cause of SIADH (Syndrome of Inappropriate Anti-Diuretic Hormone secretion). It occurs when herpesvirus type 3 activation presents in the first division, or ophthalmic division of the trigeminal nerve.

Background Early initiation of pulmonary arterial hypertension (PAH) therapies is associated with improved long-term outcomes, yet data on the early use of prostacyclin pathway agents are limited. In these post hoc analyses of the Prostacyclin (PGI2) Receptor Agonist In Pulmonary Arterial Hypertension (GRIPHON) study, the largest randomized controlled trial for PAH to date, the prognostic value of time from diagnosis and its impact on treatment response were examined. Research Question How does time from diagnosis impact morbidity/mortality events and response to selexipag treatment in patients with PAH? Study Design and Methods The GRIPHON study randomly assigned 1,156 patients with PAH to selexipag or placebo treatment. Patients were categorized post hoc into a time from diagnosis of ≤ 6 months and > 6 months at randomization. Hazard ratios (selexipag vs placebo) were calculated for the primary end point of morbidity/mortality by time from diagnosis using Cox proportional hazard models. Results Time from diagnosis was ≤ 6 months in 34.9% and > 6 months in 65.1% of patients. Time from diagnosis was prognostic of morbidity/mortality, with newly diagnosed patients having a poorer long-term outcome than patients diagnosed for longer. Compared with placebo, selexipag reduced the risk of morbidity/mortality in patients with a time from diagnosis of ≤ 6 months and > 6 months, with a more pronounced effect in newly diagnosed patients (hazard ratio, 0.45 [95% CI, 0.33-0.63] and 0.74 [95% CI, 0.57-0.96], respectively; P = .0219 for interaction). Interpretation In the GRIPHON study, newly diagnosed PAH patients had a worse prognosis than patients with a longer time from diagnosis. The benefit of selexipag treatment on disease progression was more pronounced in patients treated earlier than in patients treated later. Trial Registry ClinicalTrials.gov ; No.: NCT01106014; URL: www.clinicaltrials.gov

Purpose Despite the commonplace use of tranexamic acid in total joint arthroplasty, much of the current data regarding its cost-effectiveness examines savings directly related to its hemostatic properties, without considering its protective effect against periprosthetic joint infections. Using break-even economic modeling, we calculated the cost-effectiveness of routine tranexamic acid administration for infection prevention in total joint arthroplasty. Materials and methods The cost of intraoperative intravenous tranexamic acid, the cost of revision arthroplasty for periprosthetic joint infections, and the baseline rates of periprosthetic joint infections in patients who did not receive intraoperative tranexamic acid were obtained from the literature and institutional purchasing records. Break-even economic modeling incorporating these variables was performed to determine the absolute risk reduction in infection rate to make routine intraoperative tranexamic acid use economically justified. The number needed to treat was calculated from the absolute risk reduction. Results Routine use of intraoperative tranexamic acid is economically justified if it prevents at least 1 infection out of 3125 total joint arthroplasties (absolute risk reduction = 0.032%). Cost-effectiveness was maintained with varying costs of tranexamic acid, infection rates, and periprosthetic joint infection costs. Conclusion The routine use of intraoperative tranexamic acid is a highly cost-effective practice for infection prevention in primary and revision total joint arthroplasty. The use of tranexamic acid is warranted across a wide range of costs of tranexamic acid, initial infection rates, and costs of periprosthetic joint infection treatment.

Background Recent case series have reported early failure with the use of high-viscosity cement (HVC) in total knee arthroplasty (TKA). We evaluated revision risk after TKA with HVC compared with medium-viscosity cement (MVC) in a large cohort. Methods We conducted a cohort study using data from Kaiser Permanente’s Total Joint Replacement Registry. Patients who underwent fully cemented primary TKA for osteoarthritis were identified (2001-2018). Only posterior-stabilized, fixed-mobility designs of the 3 highest-volume implant systems (DePuy PFC, Zimmer NexGen, and Zimmer Persona) were included to mitigate confounding from implant characteristics. Palacos (Zimmer/Heraeus) and Simplex (Stryker) cements comprised the HVC and MVC exposure groups, respectively. Propensity score–weighted Cox proportional hazards regression was used to evaluate risk for any revision during follow-up and risk for revision from aseptic loosening specifically. Results The final cohort comprised 76,052 TKAs, 41.1% using MVC. The crude 14-year cumulative revision probability was 4.55% and 5.12% for TKA with MVC and HVC, respectively. In propensity score–weighted Cox models, MVC compared with HVC had a lower risk of any revision (hazard ratio = 0.82, 95% confidence interval = 0.70-0.95) while no difference was observed for revision from aseptic loosening (hazard ratio = 0.80, 95% confidence interval = 0.56-1.13). Conclusion While we observed a lower risk for any revision with the use of Simplex MVC compared with Palacos HVC, we did not observe a difference in revision for aseptic loosening specifically. Given the widespread use of HVC, additional research to investigate other HVC and potential mechanisms for failure outside of loosening is warranted. Level of Evidence Level III.

Objectives The goal of this study was to describe outcomes of patients with bridge to heart transplantation (BTT) after changes were made to the donor heart allocation system. Background Left ventricular assist devices (LVADs) have been used as a BTT. On October 18, 2018, the donor heart allocation system in the United States was updated. Methods This study identified adults in the United Network for Organ Sharing database with durable, continuous-flow LVAD at listing or implanted while listed between April 2017 and April 2020. Baseline recipient and donor characteristics, waitlist survival, and post-transplantation outcomes were compared pre- and post-allocation system change. Results A total of 1,794 patients met inclusion criteria: 983 in the pre-change period and 814 afterward. The number of patients listed with LVAD decreased nationally over time from 102 in April 2017 to 12 in April 2020 (p Conclusions The number of patients with BTT on the transplant list decreased steadily and dramatically after the allocation system change. Although time to transplant decreased, there was an increase in post-transplant mortality. These data suggest that the risks and benefits of LVAD implantation as a BTT have changed under the new allocation system and that the appropriate indication for this treatment strategy warrants a re-evaluation.

PURPOSE: To explore the relationship between physical activity (PA) and quality of life (QOL) among Hispanic and non-Hispanic white breast cancer (BC) cases and population-based controls from the New Mexico ‘Long-Term Quality of Life Study’. METHODS: Self-reported PA (low, moderate, vigorous MET hours/week) at baseline and follow-up interviews (12–15 years) were available for 391 cases and controls and modeled using multiple linear regressions with SF-36 mean composite scores for physical and mental health. The change in PA from baseline to follow-up and interactions with ethnicity were also examined. Models were adjusted for age at diagnosis/baseline interview, education, comorbidities, body mass index, and change in PA. RESULTS: PA intensities at each timepoint did not differ by case/control status; however, the change in vigorous PA was lower among cases (p = 0.03). At follow-up, low intensity PA increased mental health QOL scores among cases; however, the interaction between low intensity PA and ethnicity was statistically significant among controls indicating decreased mental health among Hispanics (p = 0.02). Change in moderate PA was associated with increased physical and mental health among cases (physical: β = 0.186, p = 0.008; mental: β = 0.225, p = 0.001) and controls (physical: β = 0.220, p < 0.0001; mental: β = 0.193, p = 0.002), when controlling for confounders. CONCLUSION: Our results demonstrate that all levels of PA are important for mental health among BC cases, while activities of higher intensity are important for physical health among women overall. The statistical interaction observed between ethnicity and low intensity PA among controls for mental health warrants further research to provide a meaningful interpretation.

Objective To examine the effectiveness and safety of epidural analgesia in the presurgical period in patients with hip fracture undergoing surgical repair. Design Systematic review. Methods The study protocol was registered with the PROSPERO systematic reviews registry with the (identifier CRD42019140396). Electronic databases were searched for randomized controlled trials comparing preoperative epidural analgesia with other forms of pain management in patients with a hip fracture. The primary outcomes included perioperative cardiac events and death. Pain, noncardiac complications, and adverse effects were also examined as secondary outcomes. The heterogeneity of the included studies was assessed with the I2 statistic, and a random-effects meta-analysis was conducted once sufficient homogeneity was demonstrated. Results Four studies, which included a total of 221 patients, met the inclusion criteria. Preoperative epidural analgesia resulted in fewer cardiac events, which was a reported outcome in two included studies (relative risk 0.30; 95% confidence interval 0.14–0.63; I2=0%). Preoperative epidural analgesia was also associated with a decreased perioperative mortality rate in a meta-analysis of two studies (relative risk 0.13; 95% confidence interval 0.02–0.98; I2 = 0%). Pain was not pooled because of variability in assessment methods, but preoperative epidural analgesia was associated with reduced pain in all four studies. Conclusions Preoperative epidural analgesia for hip fracture may reduce perioperative cardiac events and deaths, but the number of included studies in this systematic review was low. More research should be done to determine the benefit of early epidural analgesia for patients with hip fracture.

Background Elective total shoulder arthroplasty is highly successful, but there is a subset of patients who continue to experience pain after this procedure. The purposes of this study were to elucidate the prevalence and patient characteristics predictive of persistent pain after shoulder arthroplasty. Methods We identified patients who had received an elective primary shoulder arthroplasty (anatomic or reverse) between 2016 and 2017 from our prospectively maintained, single-surgeon registry. Patients were stratified by the presence or absence of persistent pain at 2 years postoperatively, as defined by a Visual Analog Pain score of ≥2. This value was chosen in accordance with previously reported values for minimal clinically important differences. Multivariable logistic regression was used to identify factors associated with persistent pain. Results Of the 244 patients included for analysis, 46(18.9%) had persistent pain at 2 years postoperatively. The average pain score in this group was found to be significantly greater than the patients without pain (3.6 ± 1.6 vs 0.14 ± 0.35, P Conclusion About 1 in 5 patients report persistent pain after elective primary shoulder arthroplasty. Prompt identification of at-risk patients (eg, those with severe postoperative inpatient pain and a history of prior shoulder surgery) may prove effective in optimizing the pain experience after shoulder arthroplasty. Level of evidence Level III; Cohort Study with Prospective Data and Retrospective Study Design.

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35–64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values

Background Prosthetic joint infection (PJI) is a catastrophic complication after total joint arthroplasty that exacts a substantial economic burden on the health-care system. This study used break-even analysis to investigate whether the use of silver-impregnated occlusive dressings is a cost-effective measure for preventing PJI after primary total knee arthroplasty (TKA) and total hip arthroplasty (THA). Methods Baseline infection rates after TKA and THA, the cost of revision arthroplasty for PJI, and the cost of a silver-impregnated occlusive dressing were determined based on institutional data and the existing literature. A break-even analysis was then conducted to calculate the minimal absolute risk reduction needed for cost-effectiveness. Results The use of silver-impregnated occlusive dressings would be economically viable at an infection rate of 1.10%, treatment costs of $25,692 for TKA PJI, and $31,753 for THA PJI and our institutional dressing price of $38.05 if it reduces infection rates after TKA by 0.15% (the number needed to treat [NNT] = 676) and THA by 0.12% (NNT = 835). The absolute risk reduction needed to maintain cost-effectiveness did not change with varying initial infection rates and remained less than 0.40% (NNT = 263) for infection treatment costs as low as $10,000 and less than 0.80% (NNT = 129) for dressing prices as high as $200. Conclusion The use of silver-impregnated occlusive dressings is a cost-effective measure for infection prophylaxis after TKA and THA.

Background Patients undergoing elective shoulder arthroplasty have highly variable pain experiences. We sought to characterize preoperative patient characteristics associated with fast and slow pain relief after elective total shoulder arthroplasty and evaluated whether differences in early pain recovery predicted longer term pain relief. Methods We identified 324 patients undergoing elective primary shoulder arthroplasty, reverse and anatomic, between 2015 and 2018 from our prospective registry. Postoperative pain relief was defined as the difference in preoperative and 2-week postoperative pain intensity. Three groups were then created: fast responders (top decile), slow responders (bottom decile), and normal responders. Multinomial regression was used to identify preoperative patient factors associated with either slow or fast pain responses. Results Factors associated with a fast pain response included older age and being married. A slow pain response was associated with being unmarried. Pain intensity was lower in the fast responders at 6 weeks (0.60 ± 0.80 vs. 3.4 ± 2.50, P Conclusion The postoperative pain experience after shoulder arthroplasty seems to be influenced by patient age and marital status. Patients with marginal improvement in pain relief should be counseled that their recovery may be more prolonged, but by the 1-year mark they are likely to achieve comparably low pain levels to other patients. Level of evidence Level III; Retrospective Design; Prognosis Study

The United States is experiencing an opioid epidemic, and there were more than 10 million opioid misusers aged 12 or older each year. Identifying patients at high risk of Opioid Use Disorder (OUD) can help to make early clinical interventions to reduce the risk of OUD. Our goal is to predict OUD patients among opioid prescription users through analyzing electronic health records with machine learning and deep learning methods. This will help us to better understand the diagnoses of OUD, providing new insights on opioid epidemic. Electronic health records of patients who have been prescribed with medications containing active opioid ingredients were extracted from Cerner Health Facts database between January 1, 2008 and December 31, 2017. Long Short-Term Memory (LSTM) models were applied to predict opioid use disorder risk in the future based on recent five encounters, and compared to Logistic Regression, Random Forest, Decision Tree and Dense Neural Network. Prediction performance was assessed using F-1 score, precision, recall, and AUROC. Our temporal deep learning model provided promising prediction results which outperformed other methods, with a F1 score of 0.8023 and AUCROC of 0.9369. The model can identify OUD related medications and vital signs as important features for the prediction. LSTM based temporal deep learning model is effective on predicting opioid use disorder using a patient past history of electronic health records, with minimal domain knowledge. It has potential to improve clinical decision support for early intervention and prevention to combat the opioid epidemic., Comment: 20 pages, 6 figures

Purpose Subcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a population pharmacokinetic model for subcutaneous fentanyl injection in older patients. Methods Twenty-one patients who received subcutaneous fentanyl injections (50 to 75 mu g) were recruited. Fentanyl concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. A base model was selected based on the Akaike information criterion. Age, sex, body weight, number of previous fentanyl doses, number of prescribed medications, creatinine clearance, Charlson Comorbidity Index, Identification of Seniors at Risk score and concurrent use of CYP3A4 inhibitors were covariates considered for inclusion. A p value of < 0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check. Results A one-compartment, first-order absorption with lag time and linear elimination model was the best to fit to the fentanyl concentration data. The absorption rate constant was 0.136 h(-1) (between subject variability (BSV), 46%), lag time 0.66 h (BSV 51%), apparent volume of distribution 6.28 L (BSV 30%), and apparent clearance 16.3 L.h(-1) (BSV 54%). The Charlson Comorbidity Index was the only covariate included in the final model, where a higher value of the index increased fentanyl exposure and C-max. Conclusion This is the first report of subcutaneous fentanyl population pharmacokinetic model to evaluate fentanyl pharmacokinetic in older patients. The between subject variability in clearance and subcutaneous absorption rate was relatively high, and some patients recorded high fentanyl concentrations in the context of their titration to effect. Refereed/Peer-reviewed

Background Developing a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells' proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection. Methods Using 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets. Results An exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature's negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell-mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature's negative predictive value was 90.6% and its positive predictive value was 77.8%. Conclusions Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.

Substance use and psychopathology symptoms increase in adolescence. One key risk factor for these is high parent stress. Mindfulness interventions reduce stress in adults and may be useful to reduce parent stress and prevent substance use (SU) and psychopathology in adolescents. This study tested the feasibility and effects of a mindfulness intervention for parents on adolescent SU and psychopathology symptoms. Ninety-six mothers of 11–17 year olds were randomly assigned to a mindfulness intervention for parents (the Parenting Mindfully [PM] intervention) or a brief parent education [PE] control group. At pre-intervention, post-intervention, 6-month follow-up, and 1-year follow-up, adolescents reported on SU and mothers and adolescents reported on adolescent externalizing and internalizing symptoms. Primary intent to treat analyses found that the PM intervention prevented increases in adolescent SU over time, relative to the PE control group. The PM intervention also prevented increases in mother-reported externalizing symptoms over time relative to the PE control group. However, PM did not have a significant effect on internalizing symptoms. PM had an indirect effect on adolescent-reported externalizing symptoms through greater mother mindfulness levels at post-intervention, suggesting mother mindfulness as a potential intervention mechanism. Notably, while mothers reported high satisfaction with PM, intervention attendance was low (31% of mothers attended zero sessions). Secondary analyses with mothers who attended > = 50% of the interventions (n = 48) found significant PM effects on externalizing symptoms, but not SU. Overall, findings support mindfulness training for parents as a promising intervention and future studies should work to promote accessibility for stressed parents. Clinical Trials Identifier: NCT02038231; Date of Registration: January 13, 2014

Introduction: To determine the publication rate of registered clinical trials evaluating therapeutic approaches for diabetic macular edema (DME). Methods: Using the search terms “Diabetic Macular Edema,” the National Institute of Health’s ClinicalTrials.gov online registry was searched to identify all clinical trials concerning DME. Non-interventional trials, terminated trials, trials not concerning DME, and those not completed between 2005 and 2015 were excluded. Publication status of each trial was determined using searches of the study title, keywords, author(s), and NCT number on PubMed.gov and Google Scholar. Results: A total of two hundred and forty-seven studies were identified in the primary analysis. Of the 97 trials meeting inclusion criteria, 60 (61.9%) were published. Late-phase trials were published at higher rate (74.5% [35/47]) than early phase trials (50% [25/50]) (p = 0.01). Trial location, date of completion, and industry involvement did not significantly affect the publication rate. Conclusion: Of the registered trials listed in the ClinicalTrials.gov registry investigating DME, 61.9% were published.