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OBJECTIVE The primary aims of this study were to identify latent profiles of acute stress disorder (ASD) symptoms and to evaluate postconcussive symptom differences across the identified profiles as measured by the Acute Stress Disorder Scale and the Military Acute Concussion Evaluation, respectively. METHOD Participants (N = 315) in the current study were predominantly active-duty (75.0%), enlisted (97.8%) males (97.4%) serving in the U.S. Army (87.8%). Approximately, half of the sample reported being married or engaged (51.1%) and was on average 25.94 (SD = 6.31) years old. Participants were referred to the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq, to be evaluated as part of routine clinical assessment for neurocognitive and psychological symptoms following exposure to a blast. RESULTS A 3-profile solution was identified as the most parsimonious and best-fitting model based on statistical model fit indices. Blast injured service members in Profile 3 had greater ASD total and subscale severity compared to the other 2 subgroups, with effect size estimates largely differing by hyperarousal and reexperiencing symptoms. Furthermore, Profiles 2 and 3 were more likely to demonstrate postconcussive symptoms compared to Profile 1. CONCLUSIONS Findings provide novel information on heterogenous ASD symptom profiles during the acute phase following a blast injury and highlight the relationship between psychological and physical symptoms. Classification of blast-injured service members may help identify at-risk individuals who would benefit from further clinical care and mitigate long-term psychological and neurocognitive issues. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Carpal tunnel syndrome (CTS), trigger finger (TF), and De Quervain tenosynovitis (DQ) are 3 common pathologies of the hand often treated with relatively simple surgical procedures. However, outcomes from these procedures can be compromised by postoperative complications. The aim of this study was to evaluate the association between diabetes, tobacco use, and obesity and the incidence of postoperative complications. Methods: We reviewed 597 patients treated surgically for CTS, TF, or DQ from 2010 to 2015. We used bivariate and multivariate analyses to assess independent associations between diabetes, tobacco use, obesity, and surgical complications and compared the incidences with healthier patients without these comorbidities. We also looked at patients with overlapping diagnoses of these comorbidities. Results: Bivariate analysis showed that patients with diabetes and smokers were more likely to have a surgical complication. Multivariate analysis showed diabetes and tobacco use as independent predictors of complications. The disease states or combinations placing patients at the highest risk of a postoperative complication were the diabetic-smoker-obese, diabetic-smoker, diabetic-obese, diabetic, and smoker-obese groups. The diabetic-smoker-obese patient population had a 42.02% predicted rate of postoperative complications. Conclusions: Diabetes and tobacco use are independent risk factors for complications after operative treatment of CTS, TF, and DQ. Obesity when coexisting with diabetes mellitus (DM) and/or tobacco use increased the risk of complications. When the 3 patient factors evaluated, DM, obesity, and tobacco use, were present, the rate of complications was 42.02%. Careful assessment and discussion should occur before proceeding with operative treatment for simple hand conditions in patients with the risk factors studied.

To determine whether multimorbidity is associated with treatment changes and achieving target disease activity thresholds in patients with active rheumatoid arthritis (RA).We conducted a retrospective cohort study of adults with active RA within the Rheumatology Informatics System for Effectiveness (RISE) registry. Multimorbidity was measured using RxRisk, a medication-based index of chronic disease. We used multivariable logistic regression models to assess the associations of multimorbidity with the odds of initiating a new disease-modifying antirheumatic drug (DMARD) in active RA, and among those initiating a new DMARD, the odds of achieving low disease activity or remission.We identified 15,626 patients using the Routine Assessment of Patient Index Data 3 (RAPID3) cohort and 5,733 patients using the Clinical Disease Activity Index (CDAI) cohort. All patients had active RA, of which 1,558 (RAPID3) and 834 (CDAI) initiated a new DMARD and had follow-up disease activity measures. Patients were middle aged, female, and predominantly White, and on average received medications from 6 to 7 RxRisk categories. Multimorbidity was not associated with new DMARD initiation in active RA. However, a greater burden of multimorbidity was associated with lower odds of achieving treatment targets (per 1-unit RxRisk: RAPID3 cohort odds ratio [OR] 0.95 [95% confidence interval (95% CI) 0.91, 0.98]; CDAI cohort OR 0.94 [95% CI 0.90, 0.99]). Those with the highest burden of multimorbidity had the lowest odds of achieving target RA disease activity (RAPID3 cohort OR 0.54 [95% CI 0.34, 0.85]; CDAI cohort OR 0.65 [95% CI 0.37, 1.15]).These findings from a large, real-world registry illustrate the potential impact of multimorbidity on treatment response and indicate that a more holistic management approach targeting multimorbidity may be needed to optimize RA disease control in these patients.

Background Asthma epidemics associated with thunderstorms have had catastrophic impacts on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. Objective We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. Methods This multi-centre study recruited adults from Melbourne (Australia) with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry, white blood-cell count, ryegrass pollen specific IgE (RGP-spIgE) and fractional exhaled nitric oxide (FeNO) were measured to identify risk factors for a history of TA in individuals with SAR. Results From a total of 228 individuals with SAR, 35% (80/228) reported SAR only (I-SAR), 37% (84/228) reported TA symptoms but had not attended hospital for treatment (O-TA) and 28% (64/228) had presented to hospital for TA (H-TA). All H-TA patients reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower forced expiratory volume in one second (FEV1) and asthma control questionnaire (ACQ) score >1.5 were associated with H-TA. Higher blood RGP-spIgE, eosinophil counts, and FeNO were significantly associated with both O-TA and H-TA. Receiver-operating curve (ROC) analysis showed RGP-spIgE >10·1 kU/L and pre-bronchodilator FEV1 ≤90% to be biomarkers of increased H-TA risk. Conclusion Clinical tests can identify risk for a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis with current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival of ATLL cells. As a single agent, the CDK6 inhibitor palbociclib induced cell cycle arrest and apoptosis in ATLL models with wild-type TP53. ATLL models that had inactivated TP53 genetically were relatively resistant to palbociclib owing to compensatory CDK2 activity, and this resistance could be reversed by APR-246, a small molecule activator of mutant TP53. The CRISPR-Cas9 screen further highlighted the dependence of ATLL cells on mTORC1 signaling. Treatment of ATLL cells with palbociclib in combination with mTORC1 inhibitors was synergistically toxic irrespective of the TP53 status. This work defines CDK6 as a novel therapeutic target for ATLL and supports the clinical evaluation of palbociclib in combination with mTORC1 inhibitors in this recalcitrant malignancy.

Background Traumatic brain injury (TBI) can precipitate new-onset psychiatric symptoms or worsen existing psychiatric conditions. To elucidate specific mechanisms for this interaction, neuroimaging is often used to study both psychiatric conditions and TBI. This systematic review aims to synthesize the existing literature of neuroimaging findings among patients with anxiety after TBI. Methods We conducted a Preferred Reporting Items for Systematic Review and Meta-Analyses–compliant literature search via PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases before May, 2019. We included studies that clearly defined TBI, measured syndromic anxiety as a primary outcome, and statistically analyzed the relationship between neuroimaging findings and anxiety symptoms. Results A total of 5982 articles were retrieved from the systematic search, of which 65 studied anxiety and 13 met eligibility criteria. These studies were published between 2004 and 2017, collectively analyzing 764 participants comprised of 470 patients with TBI and 294 non-TBI controls. Imaging modalities used included magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, electroencephalogram, magnetic resonance spectrometry, and magnetoencephalography. Eight of 13 studies presented at least one significant finding and together reflect a complex set of changes that lead to anxiety in the setting of TBI. The left cingulate gyrus in particular was found to be significant in 2 studies using different imaging modalities. Two studies also revealed perturbances in functional connectivity within the default mode network. Conclusions This is the first systemic review of neuroimaging changes associated with anxiety after TBI, which implicated multiple brain structures and circuits, such as the default mode network. Future research with consistent, rigorous measurements of TBI and syndromic anxiety, as well as attention to control groups, previous TBIs, and time interval between TBI and neuroimaging, are warranted. By understanding neuroimaging correlates of psychiatric symptoms, this work could inform future post-TBI screening and surveillance, preventative efforts, and early interventions to improve neuropsychiatric outcomes.

Background US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness. Research Question What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries? Study Design And Methods Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay. Results We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P Interpretation Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths.

Objective The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation. Methods Three bovine aortic valves were mounted asymmetrically in a previously validated 3–dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left–right commissure, and the left and right coronary cusps were sewn together. The left–right commissure was then detached and reimplanted 10 mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair. Results The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6% ± 3.4%; P = .037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3 ± 18.3 cm/sec versus 325.3 ± 58.2 cm/sec (P = .29), 34.3 ± 4.2 mm Hg versus 43.3 ± 15.4 mm Hg (P = .30), and 11 ± 1 mm Hg versus 9.3 ± 2.5 mm Hg (P = .34), respectively. Conclusions An ex vivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.

OBJECTIVE: Electronic health record (EHR) patient portals were promoted to enhance patient engagement. However, organizations often deny patient access to records of treatment for mental health disorders. This study explores patient and provider experience of patient electronic access to the mental health treatment record and the use of secure messaging. METHODS: Online surveys of a sample of mental health patients (N=168) and providers (N=80) addressed their experience using patient portals and secure messaging. RESULTS: Only 29 of the 80 providers (36%) worked at organizations which provided patients electronic access to mental health records. Of these 29 providers, 72% endorsed that patients requested a change in the provider note, 69% endorsed patients asked more questions, 55% endorsed patients reported they experienced significant distress after accessing portal, and 21% reported patients engaged in negative and/or self-destructive behavior towards themselves or others. Of patients with access to mental health notes (N=37), 86% endorsed that they gained a better understanding of what was discussed in the appointment, 84% trusted their healthcare provider more, 76% felt comforted or relieved after reading their health information, and 57% reported they were better able to take medications as prescribed. Both patients and providers enjoyed the efficiency of secure messaging. Open text responses are also presented. CONCLUSIONS: The implementation of electronic access to mental health notes requires a transition from viewing the medical record as the exclusive tool of providers to that of a collaborative tool for patients and providers to achieve treatment goals.

OBJECTIVE Chronic adhesive spinal arachnoiditis (SA) is a complex disease process that results in spinal cord tethering, CSF flow blockage, intradural adhesions, spinal cord edema, and sometimes syringomyelia. When it is focal or restricted to fewer than 3 spinal segments, the disease responds well to open surgical approaches. More extensive arachnoiditis extending beyond 4 spinal segments has a much worse prognosis because of less adequate removal of adhesions and a higher propensity for postoperative scarring and retethering. Flexible neuroendoscopy can extend the longitudinal range of the surgical field with a minimalist approach. The authors present a cohort of patients with severe cervical and thoracic arachnoiditis and myelopathy who underwent flexible endoscopy to address arachnoiditis at spinal segments not exposed by open surgical intervention. These observations will inform subsequent efforts to improve the treatment of extensive arachnoiditis. METHODS Over a period of 3 years (2017–2020), 10 patients with progressive myelopathy were evaluated and treated for extensive SA. Seven patients had syringomyelia, 1 had spinal cord edema, and 2 had spinal cord distortion. Surgical intervention included 2- to 5-level thoracic laminectomy, microscopic lysis of adhesions, and then lysis of adhesions at adjacent spinal levels performed using a rigid or flexible endoscope. The mean follow-up was 5 months (range 2–15 months). Neurological function was examined using standard measures. MRI was used to assess syrinx resolution. RESULTS The mean length of syringes was 19.2 ± 10 cm, with a mean maximum diameter of 7.0 ± 2.9 mm. Patients underwent laminectomies averaging 3.7 ± 0.9 (range 2–5) levels in length followed by endoscopy, which expanded exposure by an average of another 2.4 extra segments (6.1 ± 4.0 levels total). Endoscopic dissection of extensive arachnoiditis in the dorsal subarachnoid space proceeded through a complex network of opaque arachnoidal bands and membranes bridging from the dorsal dura mater to the spinal cord. In less severely problematic areas, the arachnoid membrane was transparent and attached to the spinal cord through multifocal arachnoid adhesions bridging the subarachnoid space. The endoscope did not compress or injure the spinal cord. CONCLUSIONS Intrathecal endoscopy allowed visual assessment and safe removal of intradural adhesions beyond the laminectomy margins. Further development of this technique should improve its effectiveness in opening the subarachnoid space and untethering the spinal cord in cases of extensive chronic adhesive SA.

[ ]lessons learned from previous pandemics helped catalyze COVID19 preparedness in several countries 2 Scientists in China identified and shared genetic sequencing of SARS-CoV-2 on January 10, allowing international jump starts in testing technology (South Korea) and vaccine development (e g , United States, United Kingdom) [ ]of the 2015 SARS (severe acute respiratory syndrome) epidemic, South Korea established the Infectious Disease Control Center, which later distributed COVID-19 testing guidelines before the first confirmed South Korean case 2 Responses in Hong Kong, Taiwan, and South Korea used technology- including mobile phone data, credit card records, and closed-circuit TV recordings-to help identify, isolate, and contact trace COVID-19-positive individuals 2 Despite encroachment on individual privacy and liberties, public recall of SARS and MERS (Middle East respiratory syndrome) facilitated adherence to these procedures 2 Unlike the fragmented US health care system, universal health care access in all other developed nations facilitated support of pandemic responses [ ]strong central coordination is essential to COVID-19 mitigation and precision public health

An often overlooked element of pulmonary vascular disease is time. Cellular responses to time, which are regulated directly by the core circadian clock, have only recently been elucidated. Despite an extensive collection of data regarding the role of rhythmic contribution to disease pathogenesis (such as systemic hypertension, coronary artery, and renal disease), the roles of key circadian transcription factors in pulmonary hypertension remain understudied. This is despite a large degree of overlap in the pulmonary hypertension and circadian rhythm fields, not only including shared signaling pathways, but also cell-specific effects of the core clock that are known to result in both protective and adverse lung vessel changes. Therefore, the goal of this review is to summarize the current dialogue regarding common pathways in circadian biology, with a specific emphasis on its implications in the progression of pulmonary hypertension. In this work, we emphasize specific proteins involved in the regulation of the core molecular clock while noting the circadian cell-specific changes relevant to vascular remodeling. Finally, we apply this knowledge to the optimization of medical therapy, with a focus on sleep hygiene and the role of chronopharmacology in patients with this disease. In dissecting the unique relationship between time and cellular biology, we aim to provide valuable insight into the practical implications of considering time as a therapeutic variable. Armed with this information, physicians will be positioned to more efficiently use the full four dimensions of patient care, resulting in improved morbidity and mortality of pulmonary hypertension patients.

The recombinant, live, attenuated, tetravalent dengue vaccine CYD-TDV has shown efficacy against all four dengue serotypes. In this exploratory study (CYD59, NCT02827162), we evaluated potential associations of host human leukocyte antigen (HLA) alleles with dengue antibody responses, CYD-TDV vaccine efficacy, and virologically-confirmed dengue (VCD) cases. Children 4-11 years old, who previously completed a phase 2b efficacy study of CYD-TDV in a single center in Thailand, were included in the study. Genotyping of HLA class I and II loci was performed by next-generation sequencing from DNA obtained from 335 saliva samples. Dengue neutralizing antibody titers (NAb) were assessed as a correlate of risk and protection. Regression analyses were used to assess associations between HLA alleles and NAb responses, vaccine efficacy, and dengue outcomes. Month 13 NAb log geometric mean titers (GMTs) were associated with decreased risk of VCD. In the vaccine group, HLA-DRB1*11 was significantly associated with higher NAb log GMT levels (beta: 0.76; p = 0.002, q = 0.13). Additionally, in the absence of vaccination, HLA associations were observed between the presence of DPB1*03:01 and increased NAb log GMT levels (beta: 1.24; p = 0.005, q = 0.17), and between DPB1*05:01 and reduced NAb log GMT levels (beta: -1.1; p = 0.001, q = 0.07). This study suggests associations of HLA alleles with NAb titers in the context of dengue outcomes. This study was registered with clinicaltrials.gov: NCT02827162.

Background Use of routine chest x-rays (CXR) following thoracostomy tube (TT) removal is highly variable and its utility is debated. We hypothesize that routine post-pull chest x-ray (PP-CXR) findings following TT removal in pediatric trauma would not guide the decision for TT reinsertion. Methods Patients ≤ 18 y who were not mechanically ventilated and undergoing final TT removal for a traumatic hemothorax (HTX) and/or pneumothorax (PTX) at a level I pediatric trauma center from 2010 to 2020 were retrospectively reviewed. The outcomes of interest were rate of PP-CXR and TT reinsertion rate following PP-CXR. Clinical predictors for worsened findings on PP-CXR were also assessed. Results Fifty-nine patients were included. A CXR after TT removal was performed in 57 patients (97%), with 28% demonstrating worsened CXR findings compared to the prior film. Except for higher ISS (p = 0.033), there were no demographic or clinical predictors for worsened CXR findings. However, they were more likely to have additional films following the TT removal (p = 0.008) than those with stable or improved PP-CXR findings. One (1.8%) asymptomatic child with worsened PP-CXR findings had TT reinsertion based purely on their worsened PP-CXR findings. Conclusions The vast majority of PP-CXR did not guide TT reinsertion after pediatric thoracic trauma. Treatment algorithms may aid to reduce variability and potentially unnecessary routine films.

Purpose To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). Design Observational extension study of a randomized, sham-controlled trial. Participants Two hundred twelve participants with bilateral large drusen. Methods The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. Main Outcome Measures Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. Results Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.36–1.09; P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD; P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34; 95% CI, 0.16–0.71; P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81; 95% CI, 0.67–4.88; P = 0.239). Conclusions A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.

Background A Resuscitation Plan is a medically authorised order to use or withhold resuscitation interventions. Absence of appropriate resuscitation orders exposes patients to the risk of invasive medical interventions that may be of questionable benefit depending on individual circumstances. Aims To describe among junior doctors: (1) self-reported confidence discussing and completing resuscitation plans; (2) knowledge of resuscitation policy including whether resuscitation plans are legally enforceable and key triggers for completion; and (3) the factors associated with higher knowledge of triggers for completing resuscitation plans. Methods A cross-sectional survey was conducted at five hospitals. Junior doctors on clinical rotation were approached at scheduled training sessions, before or after ward rounds, or at change of rotation orientation days and provided with a pen-and-paper survey. Results A total of 118 junior doctors participated. Most felt confident discussing (79%, n = 92) and documenting (87%, n = 102) resuscitation plans with patients. However, only 45% of doctors (n = 52) correctly identified that resuscitation plans are legally enforceable medical orders. On average, doctors correctly identified 6.8 (SD = 1.8) out of 10 triggers for completing a resuscitation plan. Doctors aged >30 years were four times more likely to have high knowledge of triggers for completing resuscitation plans (OR 4.28 (95% CI 1.54 to 11.89), p = 0.0053). Conclusion Most junior doctors feel confident discussing and documenting resuscitation plans. There is a need to improve knowledge about legal obligations to follow completed resuscitation plans, and about when resuscitation plans should be completed to ensure they are completed with patients who are most at risk. This article is protected by copyright. All rights reserved.

BACKGROUND: As treatments improve for colorectal cancer (CRC), interventions to improve quality of life and decrease long-term effects are needed. Physical activity (PA) is particularly important during cancer treatment because it may decrease treatment side effects, allow patients to more easily increase PA after treatment, and integrate with individuals’ motivation to make lifestyle changes after a cancer diagnosis. OBJECTIVES: This article aims to synthesize what is known about PA during CRC treatment. METHODS: A systematic literature search was conducted. Data were evaluated across 17 studies with a collective sample size of 1,184. Because of heterogeneity across studies, a narrative synthesis was conducted. FINDINGS: Studies included mostly college educated and married White men and women aged 50–60 years. Promising effects of PA were identified on several types of outcomes. The most common techniques to support PA included goal setting and providing instructions. The benefits of PA and how to best support PA during CRC treatment need to be better understood in future studies of racially and ethnically diverse patients with CRC.

Osteoporosis is one of the most common skeletal diseases, but current therapies are limited to generalized antiresorptive or anabolic interventions, which do not target regions that would benefit from improvements to skeletal health. To improve the evaluation of treatment plans, we used a spatio-temporal multiscale approach that combines longitudinal in vivo micro-computed tomography (micro-CT) and in silico subject-specific finite element modeling to quantitatively map bone adaptation changes due to disease and treatment at high resolution. Our findings show time and region-dependent modifications in bone remodelling following one and two sets of mechanical loading and/or pharmacological interventions. The multiscale results highlighted that the distal section was unaffected by mechanical loading alone but the proximal tibia had the greatest gain from positive interactions of combined therapies. Mechanical loading abated the catabolic effect of PTH, but the main benefit of combined treatments occurred from the additive interactions of the two therapies in periosteal apposition. These results provide detailed insight into the efficacy of combined treatments, facilitating the optimisation of dosage and treatment duration in preclinical mouse studies, and the development of novel interventions for skeletal diseases. Statement of Significance Combined mechanical loading and pharmacotherapy have the potential to slow osteoporosis-induced bone loss but current therapies do not target the regions in need of strengthening. We show for the first time spatial region-dependant interactions between PTH and mechanical loading treatment in OVX mouse tibiae, highlighting local regions in the tibia that benefitted from separate and combined treatments. Combined experimental-computational analysis also detailed the lasting period of each treatment per location in the tibia, the extent of positive (or negative) interactions of the combined therapies, and the impact of each treatment on the regulation of bone adaptation spatio-temporally. This approach can be used to create hypothesis about the interactions of different treatments to optimise the design of biomaterials and medical interventions.

Introduction: An early detection of impaired functional performance is critical to enhance symptom management for patients with chronic obstructive pulmonary disease (COPD). However, conventional functional measures based on walking assessments are often impractical for small clinics where the available space to administrate gait-based test is limited. This study examined the feasibility and effectiveness of an upper-extremity frailty meter (FM) in identifying digital measures of functional performance and assessing frailty in COPD patients. Methods: Forty-eight patients with COPD (age = 68.8 ± 8.5 years, body mass index [BMI] = 28.7 ± 5.8 kg/m2) and 49 controls (age = 70.0 ± 3.0 years, BMI = 28.7 ± 6.1 kg/m2) were recruited. All participants performed a 20-s repetitive elbow flexion-extension test using a wrist-worn FM sensor. Functional performance was quantified by FM metrics, including speed (slowness), range of motion (rigidity), power (weakness), flexion and extension time (slowness), as well as speed and power reduction (exhaustion). Conventional functional measures, including timed-up-and-go test, gait and balance tests, and 5 repetition sit-to-stand test, were also performed. Results: Compared to controls, COPD patients exhibited deteriorated performances in all conventional functional assessments (d = 0.64–1.26, p < 0.010) and all FM metrics (d = 0.45–1.54, p < 0.050). FM metrics had significant agreements with conventional assessment tools (|r| = 0.35–0.55, p ≤ 0.001). FM metrics efficiently identified COPD patients with pre-frailty and frailty (d = 0.82–2.12, p < 0.050). Conclusion: This study proposes the feasibility of using a 20-s repetitive elbow flexion-extension test and wrist-worn sensor-derived frailty metrics as an alternative and practical solution to evaluate functional performance in COPD patients. Its simplicity and low risk for test administration may also facilitate its application for remote patient monitoring. Furthermore, in settings where the administration of walking test is impractical, for example, when ventilator support is needed or space is limited, FM may be used as an alternative solution. Future studies are encouraged to use the FM to quantitatively monitor the progressive decline in functional performance and quantify outcomes of rehabilitation interventions.

BACKGROUND Health promotion is necessary to mitigate the negative consequences of colorectal cancer and its treatment. Rates of behavior modification are low in populations of cancer patients. Studies are needed to determine the factors, such as decisional conflict, which influence adoption of healthy behaviors following a cancer diagnosis. OBJECTIVE To examine the effects of information provision, decision self-efficacy, and decisional conflict on the adoption of healthy behaviors among patients with colorectal cancer. METHODS This cross-sectional study focused on 251 patients with colorectal cancer in South Korea. Information provision, decision self-efficacy, and decisional conflict were measured using validated instruments. Patients rated their decisional conflict related to the adoption of behaviors that include regular exercise and a balanced diet. RESULTS Most participants (73%) reported low satisfaction with the amount of information received. Of the participants, 64% had low decision self-efficacy, and 80% experienced decisional conflict. The perception of a higher level of information provision was associated with greater decision self-efficacy (odds ratio, 4.63; 95% confidence interval, 1.61-13.35). Higher decision self-efficacy was associated with lower decisional conflict (odds ratio, 5.19; 95% confidence interval, 2.33-11.59). CONCLUSION Receiving adequate information is important for promoting patients' confidence in making decisions about their health and reducing decisional conflict in the adoption of healthy lifestyle changes following a cancer diagnosis. IMPLICATION FOR PRACTICE Oncology nurses should assess patient information needs and promote decision self-efficacy, thus empowering patients diagnosed with colorectal cancer to make lifestyle decisions that improve their health and quality of life.

BACKGROUND In May 2018, the US Preventive Services Task Force (USPSTF) recommended prostate cancer (PCa) screening for ages 55-69 be an individual decision. This changed from the USPSTF's May 2012 recommendation against screening for all ages. The effects of the 2012 and 2018 updates on pathologic outcomes after prostatectomy are unclear. METHODS This study included 647 patients with PCa who underwent prostatectomy at our institution from 2005 to 2018. Patient groups were those diagnosed before the 2012 update (n = 179), between 2012 and 2018 updates (n = 417), and after the 2018 update (n = 51). We analyzed changes in the age of diagnosis, pathologic Gleason grade group (pGS), pathologic stage, lymphovascular invasion (LVI), and favorable/unfavorable pathology. Multivariable logistic regression adjusting for pre-biopsy covariables (age, prostate-specific antigen [PSA], African American race, family history) assessed impacts of 2012 and 2018 updates on pGS and pathologic stage. A p

Objectives Australian guidelines for dementia cover 109 recommendations for dementia care. Knowing which recommendations to implement poses a challenge for general practitioners (GPs). This study aimed to gather general practice perspectives of priority recommendations for GPs in their practice. Methods To explore which recommendations are most important and those requiring the greatest support in GP implementation, a Delphi study was conducted. Thirty-six GPs, 4 practice nurses and 1 medical services director completed two rounds of email questionnaires. Results Recommendations requiring support for GP implementation relate to early assessment of behavioural and psychological symptoms; mental health interventions tailored to the person's preferences and abilities; language and cultural barriers in access to information and services; and cognitive and learning needs in treatment delivery. Conclusion It is critical to understand where support may be needed for GPs to successfully implement recommendations to improve care provided to people with dementia and their carers.

Background Aneurysmal subarachnoid hemorrhage (aSAH) and traumatic subarachnoid hemorrhage (tSAH) differ significantly in their mortality and management. Although computed tomography angiography (CTA) is critical to guide timely interventions in aSAH, it lacks recognized benefit in assessing tSAH. Despite this, CTA commonly is included in tSAH evaluation. Objective Determine if any clinically significant cerebral aneurysms are identified on CTA in emergency department (ED) patients with a tSAH. Methods Retrospective observational study of consecutive blunt head trauma patients ages ≥ 16 years with Glasgow Coma Scale score (GCS) ≥ 13 who presented to an academic ED (100,000 annual visits) over a 7-year period. Those included had a CT-diagnosed SAH and underwent head CTA. The primary endpoint was the detection of any clinically significant brain aneurysms. Results There were 297 patients that met the inclusion criteria. Twenty-six patients (8.8%) had an incidental aneurysm discovered; one underwent elective outpatient intervention. Aneurysm-positive patients were more likely to be female (69.2% vs. 46.9%, p = 0.003), age 60 years or older (80.8% vs. 52.4%, p = 0.005), and be on anticoagulation (42.3% vs. 28.0%, p = 0.03). There were no differences between the aneurysm-positive and -negative patients with respect to GCS, history of hypertension, or mechanism of injury. Conclusions In this 7-year retrospective chart review, CTA in patients with tSAH and GCS ≥ 13 did not reveal any clinically relevant cerebral aneurysms. One incidental aneurysm later underwent outpatient neurovascular intervention. In the absence of specific clinical concerns, CTA has minimal value in well-appearing patients with a tSAH.

Purpose Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. Methods Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. Results It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. Conclusion Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction.A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report.This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement.All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups. SARS-CoV-2 infection can cause COVID-19, which is usually a mild disease in children. However, severe illness requiring intensive care management can occur, particularly in younger children and those with chronic disease. The immune system likely plays an important role in susceptibility to severe disease, but few studies have examined the immune response in infants with severe COVID-19. Here, we provide an in-depth analysis of the clinical features and immune response over time in a 5-month-old infant with congenital heart disease and severe COVID-19. Robust immune responses were observed up to 3 months following infection, providing evidence of durable and long-lived immunity against SARS-CoV-2. These findings provide important insights into the immune responses of a young infant with severe COVID-19 and might help inform future research into therapeutic targets. Wurzel et al. describe the kinetics of the immune response in relation to clinical and virological features in a 5-month old infant with congenital heart disease and severe COVID-19. The immune response was characterised by an elevated inflammatory response in the acute phase of infection, followed by Th2 skewing and prolonged T cell activation.

The objective of this systematic review is to examine metabolic dysfunction, specifically metabolic syndrome and its components, as well as type 2 diabetes mellitus (T2DM) as it relates to individuals with a diagnosis of Autism Spectrum Disorder (ASD). We searched PubMed, Embase, Cochrane, PsychInfo, and Scopus from January 1, 1998 to October 12, 2018 for English, peer-reviewed, original articles containing adult and pediatric populations with any form of ASD and metabolic dysfunction, including T2DM, hyperglycemia, hypertension, dyslipidemia, or central obesity. Exclusion criteria included studies without ASD-specific results, basic science research, review papers, case studies, and medication clinical trials. Eight studies were included in this review, with a total of 70,503 participants with ASD and 2,281,891 in comparison groups. Within ASD populations, higher prevalence for metabolic syndrome components hyperglycemia, hypertension, and dyslipidemia were observed, as well as increased incidence and prevalence of T2DM. However, heterogeneity of study definitions and measurements should be noted. While there is evidence of increased prevalence of T2DM, hyperglycemia, hypertension, and dyslipidemia for those with ASD, the relationship is poorly understood. There is also lack of research investigating central obesity and risk of metabolic syndrome as a diagnosis. More research addressing these gaps is warranted to evaluate the risk of metabolic dysfunction in populations with ASD.

In general, IBD increases arteriovenous thromboembolic events, though the association between UC and cerebrovascular complications remains inconclusive. Some studies suggest young women with UC have an increased risk of cerebrovascular accidents (CVA). The focus of this study was to characterize the rates, anatomic distribution, and risk factors for CVA in patients with UC. We developed a retrospective cohort of patients with UC at a single health care system from June 2010 to June 2015. Neuroimaging was used to document presence, location and type of stroke and traditional risk factors were considered. Prevalence of CVAs in patients with UC was compared to that of the general population of Minnesota (MN) and the United States (U.S.). A total of 2,183 UC patients were identified (1088 females [f-UC], 1095 males [m-UC]). The prevalence of CVA in UC patients (4.7%, 95% CI 3.9–5.6) was higher than in the U.S. (2.5–2.7%, p

BackgroundDirect biomarkers such as phosphatidylethanol (PEth) have the capability to detect heavy alcohol use, but it is unclear how strongly self-reported reduction in alcohol use correlates with reduction in PEth. We sought to explore the strength of correlation between reductions in self-reported alcohol use and change in PEth among a sample of women living with HIV (WLWH) who participated in a clinical trial to reduce heavy alcohol use. We also sought to determine whether this correlation was stronger in women with lower body mass index (BMI) and women without an alcohol use disorder (AUD).Methods81 WLWH (mean age=48.7, 80% Black) engaging in a randomized trial of naltrexone versus placebo with a positive baseline PEth (≥8ng/ml), and alcohol use data at baseline, 2, and 7months were included in this analysis. Spearman correlation coefficients were compared to measure the correlation between baseline PEth and number of drinks per week by demographic, biological, and alcohol use factors. Mini-International Neuropsychiatric Interview was used to screen for AUD. Further analyses were stratified by BMI and AUD. Spearman correlation coefficients were calculated for the change in PEth and the change in number of drinks per week over 7months, including 3 time-points: baseline, 2, and 7months.ResultsAt baseline, the correlation between baseline PEth and the number of drinks per week was significantly stronger for those with a BMI ≤25 compared to those with a BMI>25 (r=0.66; r=0.26, respectively). Similarly, the correlation between baseline PEth and number of drinks was stronger for those who did not screen positive for AUD compared with those who did (r=0.66; r=0.25, respectively). When stratifying by BMI, a low-to-moderate correlation (r=0.32, p=0.02) was present for persons with a BMI>25; when stratifying by AUD, a moderate correlation (r=0.50, p&nbsp

PubMed: 31209238, The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. © 2019, The Author(s)., National Institute for Health Research, NIHR Wellcome Trust, WT: 102696, 206194 Magyar Tudományos Akadémia, MTA Bayer 668858 PrECISE AstraZeneca, We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194)., Competing interests: K.C.B., Z.G., G.Y.D., E.K.Y.T., S.F., and J.R.D. are AstraZeneca employees. K.C.B., Z.G., E.K.Y.T., S.F., and J.R.D. are AstraZeneca shareholders. Y.G. receives personal compensation from Eli Lilly and Company, is a shareholder of Cleerly, Inc., and Ann Arbor Algorithms, Inc. M.G. receives research funding from AstraZeneca and has performed consultancy for Sanofi. The remaining authors declare no competing interests.

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts.METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts.RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts.CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies.

OBJECTIVES: The ProtecT (Prostate testing for cancer and Treatment) trial randomised 1,643 men with localised prostate cancer (PCa) to active monitoring, radical prostatectomy or radical radiotherapy. At 10-year median follow-up there were no differences in mortality between groups, but men receiving radical treatment had their disease progression reduced by half. We tested the hypothesis that the baseline clinico-pathological features of men who progressed (n=198) were different from those with stable disease (n=1,409).PATIENTS AND METHODS: We stratified the participants' cohort at baseline according to risk of progression using clinical disease stage, pathological grade and PSA, using Cox proportional hazard models.RESULTS: The findings demonstrated that 34% (n=505) of men had intermediate or high-risk disease, and 66% (n=973) had low-risk PCa. Of 198 men who progressed, 101 (51%) had baseline International Society of Urological Pathology (ISUP) Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5% respectively for 1,409 men without progression (pCONCLUSIONS: We demonstrate that one-third of the ProtecT cohort consists of intermediate / high risk disease, and the outcomes data at an average of 10-years follow-up are generalisable beyond men with low-risk PCa.

Here, we report a case of a 3-year-old female who presented to clinic with an enlarging mass in the posterior cervical midline. The mass was present since birth and demonstrated no cutaneous stigmata. Plain film, CT, and MRI of the cervical spine (C3-C5) revealed enlargement of the spinal canal, soft tissue calcification, spinal dysraphism, and an intramedullary, predominantly fatty, mass. The mass had associated calcifications and a highly proteinaceous cyst. Surgical resection of the spinal lesion was subsequently performed. Histopathological evaluation revealed a mature teratoma. Cervical spinal teratomas in the pediatric population are rare entities with few cases currently reported in the literature. We conducted a systematic review to outline the current evidence detailing cases of intramedullary spinal cord teratomas. Six articles were included for final review. All patients in the included articles underwent maximal surgical resection with one patient also receiving chemotherapy and radiation. With our report, we aim to add to the literature on cervical intramedullary spinal cord teratomas in the pediatric population.

Rheumatoid arthritis (RA) and its treatments are associated with an increased risk of infection, but it remains unclear whether these factors have an impact on the risk or severity of COVID-19. The present study was undertaken to assess the risk and severity of COVID-19 in a US Department of Veterans Affairs (VA) cohort of patients with RA and those without RA.A matched cohort study using national VA data was conducted. Patients diagnosed as having RA were identified among nondeceased individuals who were active in the VA health care system as of January 1, 2020 and who had received care in a VA medical center in 2019; patients for whom no RA diagnostic code was indicated were matched to the RA patients (1:1) by age, sex, and VA site (non-RA controls). Patients diagnosed as having COVID-19 and those with severe COVID-19 (defined as requiring hospitalization or leading to death) were ascertained from a national VA COVID-19 surveillance database through December 10, 2020. Multivariable Cox models were used to compare the risk of COVID-19 and COVID-19 hospitalization or death between RA patients and non-RA controls, after adjusting for demographic characteristics, comorbidities, health care utilization and access, and county-level COVID-19 incidence rates.This VA cohort of RA patients and non-RA controls (n = 33,886 subjects per group) predominantly comprised male patients (84.5%), and the mean age was 67.8 years. During follow-up, 1,503 patients in the cohort were diagnosed as having COVID-19; among them, 388 patients had severe COVID-19 (hospitalization or death), while in 228 patients, the deaths were not related to COVID-19. In the multivariable model, RA was associated with a higher risk of COVID-19 (adjusted hazard ratio [HR] 1.25 [95% confidence interval (95% CI) 1.13-1.39]) and a higher risk of COVID-19 hospitalization or death (adjusted HR 1.35 [95% CI 1.10-1.66]) as compared to non-RA controls. Use of disease-modifying antirheumatic drugs and prednisone, as well as self-reported Black race, self-reported Hispanic ethnicity, and presence of several chronic conditions, but not seropositivity for RA autoantibodies, were each associated with risk of COVID-19 and severe COVID-19 (hospitalization or death).Patients with RA are at higher risk of developing COVID-19 and severe COVID-19 (leading to hospitalization or death) compared to those without RA. With a risk of COVID-19 that approaches that of other recognized chronic conditions, these findings suggest that RA patients should be prioritized for COVID-19 prevention and management strategies.

Frozen section evaluation of head and neck squamous cell carcinoma (SCC) is critical for margin status and subsequent patient therapy. In this study, we retrospectively reviewed the rate of frozen-permanent section discrepancies in blocks with two frozen section levels compared to ≥ three levels in oral cavity and oropharyngeal SCCs. A search of the cases with both intraoperative frozen sections and corresponding permanent sections for SCCs in the oral cavity and oropharynx was performed. Frozen sections and permanent slides were compared. The nature of discrepancies was assigned to one of the following: change in diagnosis, margin status, or distance of the tumor from the margin. The cause of the discrepancy was designated as one of the following: block sampling, gross sampling, interpretation, or technical error. The pathologist experience, frozen section technical experience, and intraoperative impact of each discrepancy were also evaluated. A total of 654 frozen and corresponding permanent blocks were assessed. For 532 of the frozen section blocks, two levels were cut, while 122 frozen section blocks had ≥ three levels. Thirty-five frozen-permanent section discrepancies were observed (5.4% of all blocks). Among these, 2.5% had a possible or definitive intraoperative impact. The percentage of discrepancies in the ≥ three levels group (5.7%) was slightly higher than the two-level group (5.3%), and this difference was not statistically significant. For the two-level group, the overall block sampling error rate was 4.5%. This was not significantly different from the 4.1% block sampling error rate seen in the ≥ three levels group. The rate of block sampling discrepancy did not show significant differences based on attending or frozen section technical experience. A change in margin distance (closer margin detected on permanent) occurred in 4% of the blocks and involved 16% of the patients. This review of oral cavity and oropharynx SCCs frozen/permanent section discrepancies shows that the error rate is not significantly different depending on the number of levels cut. The results suggest that always performing more than two frozen section levels may not yield a decreased discrepancy rate. A change in margin distance occurred quite frequently, but only in rare cases it had a definitive impact on the intraoperative management. Given the importance of correct intraoperative diagnosis in patient management, additional levels may be warranted depending on the clinical scenario.

Cardiac involvement in light-chain (AL) amyloidosis has a high mortality. Once cardiac symptoms are present, it is important to make a diagnosis as there is an inverse relationship between mortality and time of diagnosis. Echocardiography is usually one of the first tests performed. But strain analysis, which can provide important clues, is not routinely performed. This is a case of AL amyloidosis presenting with heart failure in which echocardiographic strain analysis was vital for its diagnosis.

The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism presents uncommonly to primary care providers (PCPs), who often fail to recognize the subtle signs. The average age at diagnosis for common TS and TSM karyotype is 5.4 years, averaging 7.3 years. Often genetic confirmation, management, and recommended surveillance are delayed. Oftentimes, the PCP suspects a genetic etiology of an unusual phenotype, such as pinna placement or other unusual ear configurations, webbed neck with low posterior hairline, wide-spaced nipples, or short stature among other presentations. The PCP or geneticist orders diagnostic studies to confirm the diagnosis, such as a karyotype. After diagnosis, the PCP refers to the geneticist who initiates surveillance and makes recommendations for management. There are potential neurocognitive, cardiovascular, renal, reproductive, and endocrine issues. Treatment literature is vague and parental concerns are linked to quality mental health and quality of life for the family member with TS or TSM. The purpose of this article was to use a case study to introduce the topic of TS and TSM and to assist the PCP in the identification and management of patient and family concerns.

Background and Aims No consensus exists on defining intestinal ultrasound response, transmural healing, or transmural remission in inflammatory bowel disease, nor clear guidance for optimal timing of assessment during treatment. This systematic review and expert consensus study aimed to define such recommendations, along with key parameters included in response reporting. Methods Electronic databases were searched from inception to July 26, 2021, using pre-defined terms. Studies were eligible if at least two intestinal ultrasound [IUS] assessments at different time points during treatment were reported, along with an appropriate reference standard. The QUADAS-2 tool was used to examine study-level risk of bias. An international panel of experts [n = 18] rated an initial 196 statements [RAND/UCLA process, scale 1–9]. Two videoconferences were conducted, resulting in additional ratings of 149 and 13 statements, respectively. Results Out of 5826 records, 31 full-text articles, 16 abstracts, and one research letter were included; 83% [40/48] of included studies showed a low concern of applicability, and 96% [46/48] had a high risk of bias. A consensus was reached on 41 statements, with clear definitions of IUS treatment response, transmural healing, transmural remission, timing of assessment, and general considerations when using intestinal ultrasound in inflammatory bowel disease. Conclusions Response criteria and time points of response assessment varied between studies, complicating direct comparison of parameter changes and their relation to treatment outcomes. To ensure a unified approach in routine care and clinical trials, we provide recommendations and definitions for key parameters for intestinal ultrasound response, to incorporate into future prospective studies.

This study describes the prevalence and persistence of fatigue among a cohort of long-term non-Hodgkin lymphoma (NHL) survivors. Mailed surveys assessed quality-of-life including fatigue (SF-36) at baseline and five years. Logistic regression was used to identify factors associated with prevalence of fatigue at baseline and persistence of fatigue across timepoints. More than one-quarter (27.7%) of the 555 NHL survivors reported clinically meaningful fatigue at baseline and 18.7% reported persistent fatigue at five years. One-third (34.4%) reported clinically meaningful worsening of fatigue over time. Independent associations with persistent fatigue included female gender, less education, past chemotherapy, increased comorbidities, and posttraumatic stress symptoms (P

Objective: To assess the use of Medicare‐subsidised health services by women with and without dementia. Methods: Data from women of the 1921–26 birth cohort of the Australian Longitudinal Study on Women's Health were linked to various administrative datasets to ascertain dementia diagnosis. The use of subsidised general practitioner (GP) services (75+ health assessments [HAs], chronic disease management meetings [CDMs], multidisciplinary case conferences [MCCs]) and specialist and allied health services between 2000 and 2013 for these women was analysed using longitudinal GEE models. Results: A total of 9,683 women were included with 1,444 (15%) women identified as having dementia. Compared to women with no dementia indication, women with dementia had more yearly non‐emergency GP attendances (short [30 minutes] IRR=1.11 [1.04, 1.19]) and fewer specialist attendances (IRR=0.91 [0.85, 0.97]) and were more likely to have an emergency GP attendance (OR=2.29 [2.05, 2.57]). There were no significant differences in the odds of having either a HA or CDM or using allied health services for women with and without dementia indicators. Conclusions: The overall use of services designed to improve the prevention and coordination of the care of older people with chronic conditions was low. Women with dementia were no more likely to access these services. Implications for public health: There is underuse of some primary and allied healthcare services designed for people with complex chronic conditions. These could be better used by women with dementia to improve the management of complex comorbidities (e.g. CDMs), to prevent the onset of disability (e.g. physiotherapy), and enhance needs assessment and service access (e.g. HAs).

Purpose of review Cytomegalovirus (CMV) infection and disease are well described in the setting of secondary immunodeficiency. Less is known about CMV in the context of primary immunodeficiencies (PIDs), where inborn errors in one or more arms of the immune system result in variable degrees of CMV susceptibility. Recent findings PID presents unique challenges in the diagnosis and management of CMV disease. The clinical presentation of CMV in PID is often severe, accelerated by underlying immune dysregulation and iatrogenic immunosuppression. Here we describe the clinical significance of CMV infection in PID, the key components of immune defence against CMV and how these are affected in specific PIDs. CMV disease is under-recognized as a complication of common variable immunodeficiency (CVID). High rates of CMV end-organ disease, mortality, development of CMV resistance and prolonged antiviral use have been observed in individuals with CVID. Summary We recommend that clinicians tailor their approach to the individual based on their underlying immune deficit and maintain a high index of suspicion and low threshold for treatment. More research is required to improve stratification of CMV risk in PID, develop new diagnostic tools and manage end-organ disease in this cohort.

OBJECTIVE This study examines relations between food insecurity, inhibitory control, and body mass index (BMI) in early childhood. METHOD The sample comes from an evaluation of a state-funded prekindergarten program and includes 126 children (mean age = 4.73 yrs, female = 42%) from families with low incomes. Parents reported on their child's food insecurity. Child inhibitory control was assessed using a performance-based task, and children's height and weight were objectively collected at the same time as the inhibitory control assessment. A regression model was used to test whether inhibitory control moderated the association between food insecurity and BMI. The model included a large battery of covariates and adjusted for clustering at the classroom level. Ad hoc analyses were conducted to examine the robustness of findings to different conceptualizations of food insecurity based on the US Department of Agriculture's categories for severity. RESULTS A significant interaction revealed that inhibitory control moderated the association between food insecurity and children's BMI percentile. Investigation of the simple slopes suggested that greater food insecurity was related to a higher BMI percentile among children who demonstrated stronger inhibitory control. In addition, results from ad hoc analyses examining categories of food insecurity indicated that experiencing very low food security was also related to a higher BMI among children with average and strong inhibitory control. CONCLUSION This study makes a unique contribution to the existing literature by examining relations among food insecurity, inhibitory control, and BMI during a critical period in children's physical and brain development. Findings have implications for public health efforts to address childhood obesity among populations with low incomes.

PURPOSE This study aims to validate major bleeding (MB) cases within a cohort of new users of direct oral anticoagulants (DOACs) in Electronic health records (EHRs) from primary care in Spain (BIFAP), introducing more efficient techniques and automating the process of validation in the pharmacoepidemiologic research with EHR data as much as possible. METHODS Registered bleedings were identified in a cohort of new users of DOACs in BIFAP using ICPC 2 and ICD 9 codes; we ascertained these bleedings as MB through a validation strategy based on the MB definition from the International Society on Thrombosis and Hemostasis, which used hospitalization and critical localization as proxies. We assessed hospitalization with hospital discharge information (only available for some years and regions) and a free text-based algorithm created to identify hospitalization in EHR's clinical notes. Incidence rates (IR) of MB were evaluated by bleeding type. RESULTS The study cohort included 104 614 patients, with 274521.5 p-y of follow up. There were 6143 registered bleedings during the study period (519 intracranial bleeding - ICB, 4606 gastrointestinal bleeding - GIB, 1018 extracranial bleeding - ECB), from which 1679 were confirmed as MB (416 ICB, 1086 GIB, and 177 ECB). The free text-based semi-automatic algorithm had moderate recall (0.59), but high specificity (0.99), and precision (0.94). CONCLUSION The combination of hospitalization and critical localization is a valid approach to validate MB in EHRs with incomplete information. The use of more automatic methods for case validation instead of manual review of clinical notes is favored.

Although opioid agonist therapy (OAT) is associated with positive health outcomes, including improved HIV management, long-term retention in OAT remains low among patients with opioid use disorder (OUD). Using data from the Veterans Aging Cohort Study (VACS), we identify variables independently associated with OAT retention overall and by HIV status. Among 7,334 patients with OUD, 13.7% initiated OAT, and 27.8% were retained 12-months later. Likelihood of initiation and retention did not vary by HIV status. Variables associated with improved likelihood of retention included receiving buprenorphine (relative to methadone), receiving both buprenorphine and methadone at some point over the 12-month period, or diagnosis of HCV. History of homelessness was associated with a lower likelihood of retention. Predictors of retention were largely distinct between patients with HIV and patients without HIV. Findings highlight the need for clinical, systems, and research initiatives to better understand and improve OAT retention.

BACKGROUND Osteochondromas are the most common benign bone tumor, accounting for 36% of benign bone tumors. Often found within the appendicular skeleton, osteochondromas of the spine are rare, comprising 4% to 7% of primary benign spinal tumors. CASE SUMMARY We report a case of a solitary lumbar osteochondroma in an 18-year-old male with a history of a suprasellar pineal germinoma treated with combined chemotherapy and radiation. He underwent mass excision and partial laminectomy with the ultrasonic bone scalpel (Misonix, Farmingdale, NY, United States) at the L5 Level without the use of adjuvants. The patient returned to work and full activities without back pain at 3 mo postoperatively. CONCLUSION Osteochondromas are common tumors of the appendicular skeleton but rarely occur within the spine. This case discussion supplements current osteochondroma literature by describing an unusual presentation of this tumor.

Background: Hypertrophic cardiomyopathy (HCM) is defined as left ventricular end-diastolic maximal wall thickness (WTMax) ≥15.0 mm, without accounting for ethnicity, sex, and body size. It is well-established that Asians have smaller hearts than do Caucasians. Objectives: This study aims to examine the implications of this single absolute WTMax threshold on the diagnosis of HCM in Asians. Methods: The study consisted of 360 healthy volunteers (male: n = 174; age: 50 ± 12 years) and 114 genetically characterized patients with HCM (male: n = 83; age: 52 ± 13 years; genotype-positive, n = 39). All participants underwent cardiovascular magnetic resonance. WTMax was measured semiautomatically at end-diastole according to the standard 16 myocardial segments. Results: Healthy male volunteers had increased WTMax compared with that of female volunteers (8.4 ± 1.2 mm vs 6.6 ± 1.1 mm, respectively; P < 0.001). Conversely, WTMax was similar between male and female patients with HCM (15.2 ± 3.4 mm vs 14.7 ± 3.0 mm, respectively; P = 0.484) and between those with and without a pathogenic gene variant (P = 0.828). Using the recommended diagnostic threshold of 15.0 mm, 56 patients with HCM had WTMax 15.0 mm (specificity of 100% and sensitivity of 51%). Lowering WTMax thresholds to 10.0 mm in female patients and 12.0 mm in male patients did not affect specificity (100%) but significantly improved sensitivity (84%). Despite lower left ventricular mass, female patients with HCM demonstrated more features of adverse cardiac remodeling than did male patients: increased myocardial fibrosis, higher asymmetric ratio, and disproportionately worse myocardial strain. Conclusions: The study highlights cautious application of guideline-recommended WTMax to diagnose HCM in Asians. Lowering WTMax to account for ethnicity and sex improves diagnostic sensitivity without compromising specificity.

Background Eating disorders are amongst the deadliest of all mental disorders, however detection and early intervention rates remain extremely low. Current standardised screening questionnaires can be arduous or confronting and are ill-validated for online use, despite a universal shift to digital healthcare. The present study describes the development and pilot validation of a novel digital screening tool (the InsideOut Institute-Screener) for high risk and early stage eating disorders to drive early intervention and reduced morbidity. Methods We utilised a mixed cross-sectional and repeated measures longitudinal survey research design to assess symptom severity and recognised parameters of statistical validity. Participants were recruited through social media and traditional advertising, and through MTurk. An Eating Disorders Examination Questionnaire (EDE-Q) global score of 2.3 and assessment of eating disorder behaviours was used to determine probable ED. 1346 participants aged 14–74 (mean [SE] age 26.60 [11.14] years; 73.8% female, 22.6% male) completed the survey battery. 19% were randomised to two-week follow-up for reliability analysis. Results Strong positive correlations between the IOI-S and both the EDE-Q global (rs = .88) and SCOFF (rs = .75) total score were found, providing support for the concurrent validity of the scale. Inter-item correlations were moderate to strong (rs = .46–.73). Correlations between the IOI-S and two measures of social desirability diverged, providing support for the discriminant validity of the scale. The IOI-S demonstrated high internal consistency (α = .908, ω = .910) and excellent two-week test–retest reliability (.968, 95% CI 0.959–0.975; p ≤ 0.1). The IOI-S accurately distinguished probable eating disorders (sensitivity = 82.8%, specificity = 89.7% [AUC = .944], LR+ = 8.04, LR− = 0.19) and two stepped levels of risk. Conclusions and relevance The present study provides excellent initial support for the psychometric validity of the InsideOut Institute digital screening tool, which has the potential to streamline early intervention in the hopes of reducing current high morbidity and mortality. Further validation should be undertaken in known clinical populations. Plain English Summary Eating disorders are amongst the deadliest of all mental disorders, however detection and early intervention rates remain extremely low. The present study describes the initial psychometric validation of a novel digital screening tool (the InsideOut Institute Screener) for high risk and early stage eating disorders, for self-referral and/or use in primary care. 1346 participants aged 14–74 of all genders completed a survey battery designed to assess common parameters of statistical validity. Strong support was found for the screener’s ability to accurately measure eating disorder risk and symptomatology. The screener was highly positively correlated with a well known and extensively validated long form self-report questionnaire for eating disorder symptomatology. This study is a pilot validation and the genesis of a project that aims ultimately to drive early intervention leading to reduced morbidity and mortality rates in this illness group.

OBJECTIVE The present study was undertaken to evaluate whether the rate of incident chronic opioid use is higher in obese patients with rheumatoid arthritis (RA). METHODS Participants with RA in the FORWARD databank were asked about their use of weak and strong opioid medications on semiannual surveys. Incident chronic opioid use was defined as new reported use extending over 2 contiguous surveys (~7-12 months). Cox proportional hazards models were used to evaluate associations between body mass index (BMI) at enrollment and incident chronic opioid use (overall use and strong opioid use). Models adjusted for demographics, smoking, disease duration, RA treatments, household income, and education level. The predicted 5-year cumulative incidence was calculated from Cox models. RESULTS Among 19,794 participants, 2,802 experienced an incident episode of chronic opioid use over 93,254 person-years of follow-up. Higher BMI was associated with higher risk of chronic opioid use. Severe obesity (BMI >35 kg/m2 ) was associated with a higher risk of overall use (adjusted hazard ratio [HRadj ] 1.74 [95% confidence interval (95% CI) 1.72-2.04], P < 0.0001) and strong opioid use (HRadj 2.11 [95% CI 1.64-2.71], P < 0.001) compared to normal BMI. This association was partially explained by greater comorbidity, pain, and disability in obese groups. The attributable risk for obesity was 15% of overall opioid use and 24% of strong opioid use. CONCLUSION Obesity is associated with a substantially higher risk of incident chronic opioid use. Approximately 1 in 4 cases of incident use of strong opioids may be attributable to obesity, suggesting a major public health impact. Interventions to prevent or reduce obesity could have an important impact on the use of opioids.

High postprandial triglycerides are a strong cardiovascular disease risk factor. However, the extent triglycerides rise during daily living due to multiple meals remains poorly defined, especially in at-risk individuals. The aim of this case study was to quantify 24-h triglycerides in an individual with normal-weight obesity (NWO), metabolic syndrome (MetS), and type 2 diabetes (T2D) consuming a Western-style diet. In the morning, an indwelling catheter was inserted into a forearm vein and metabolic markers were measured hourly for 18-h and every 3-h for the last 6-h. The participants with NWO and T2D both experienced peak triglycerides ~280 mg/dL, which is considered an adverse response. The participant MetS had a similar relative change in triglycerides, but only reached 214 mg/dL. Interestingly, The participant with NWO displayed the greatest triglyceride area under the curve. Overall, we report that all three participants’ triglycerides nearly tripled with Western diet consumption, despite considerably different risk-profiles.