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Women with Alcohol use disorder (AUD) are more likely than men to have co-occurring depression, drink to cope with negative affect (NA), and cite negative affect as a contributor to relapse. Among AUD treatment seekers, low behavioral activation, NA, and reduced self-efficacy in abstaining from alcohol (e.g., in tempting situations) are relapse risk factors. This study investigated the association between behavioral activation, affective states, and self-efficacy among treatment-seeking women. Participants were 70 women (M = 40.50, SD = 11.59 years of age) with elevated depressive symptoms seeking AUD treatment. The Behavioral Activation for Depression Scale (BADS) was used to assess environmental engagement. The Alcohol Abstinence Self-Efficacy (AASE) scale was used to assess temptation to drink in contexts of positive and negative affect, and general positive and negative affect were assessed with the Positive and Negative Affect Schedule. Results indicated that behavioral activation was directly correlated with positive affect (PA; r = .62, p < .001) and inversely correlated with depression (r = -.35, p = .004), negative affect (r = -.39, p = .001), and temptation to drink in the context of negative affect (r = -.33, p = .006). After controlling for depressive symptoms, behavioral activation continued to be associated with greater general positive affect (β = .595, p < .001) and lower temptation to drink in the context of negative affect (β = -.348 p = .008). Our results suggest a nuanced association between behavioral activation, negative affect, and temptations to drink that is not accounted by depressive symptoms. Self-efficacy to abstain from drinking in a negative affect context should be considered when designing AUD interventions for women. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.

Research has consistently shown that positive psychological constructs are linked to better physical health, but few studies have examined the role that race plays in this connection. We explored whether positive self-evaluations were equally protective against upper respiratory infection for 271 African American adults and 700 European American adults in a series of virus-exposure studies. Participants were assessed at baseline for psychological functioning and physical health, quarantined and exposed experimentally to a respiratory virus, and then monitored for infection and symptoms. Regression analyses revealed significant interactions between race and multiple positive psychological factors; several factors that were helpful to European Americans were unhelpful or even harmful to African Americans. Building on past work showing cross-cultural variation in the health correlates of affect, this study provides evidence that the health benefits of positive psychological constructs may not be universal and points to the need to explore factors that underpin these observed differential patterns.

There is a relative paucity of literature on the outcomes after revision total hip arthroplasty (rTHA) in young patients. This study reports the survivorship and risk factors for re-revision in patients aged ≤55 years.We identified 354 patients undergoing aseptic nononcologic rTHA at mean follow-up of 5 years after revision, with mean age of 48 years, body mass index of 28 kg/mSixty-two patients (18%) underwent re-revision THA at the mean time of 2.5 years, most commonly for instability (37%), aseptic loosening (27%), and prosthetic joint infection (15%). The rTHA survivorship from all-cause re-revision and reoperation was 83% and 79% at 5 years, respectively. Multivariate analysis demonstrated that patients undergoing femoral component only (hazard ratio 4.8, P = .014) and head/liner exchange rTHA (hazard ratio 2.5, P = .022) as risk factors for re-revision THA.About 1 in 5 patients aged ≤55 years undergoing rTHA required re-revision THA at 5 years, most commonly for instability. The highest risk group included patients undergoing head/liner exchanges and isolated femoral component revisions.

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

Present results with remote intraoperative neural response telemetry (NRT) during cochlear implantation (CI) and its usefulness in overcoming the inefficiency of in person NRT.Case series.Tertiary academic otology practice.All patients undergoing primary or revision CI, both adult and pediatric, were enrolled.Remote intraoperative NRT performed by audiologists using a desktop computer to control a laptop in the operating room. Testing was performed over the hospital network using commercially available software. A single system was used to test all three FDA-approved manufacturers' devices.Success rate and time savings of remote NRT.Out of 254 procedures, 252 (99.2%) underwent successful remote NRT. In two procedures (0.7%), remote testing was unsuccessful, and required in-person testing to address technical issues.Both failed attempts were due to hardware failure (OR laptop or headpiece problems). There was no relation between success of the procedure and patient/surgical factors such as difficult anatomy, or the approach used for inner ear access. The audiologist time saved using this approach was considerable when compared with in-person testing.Remote intraoperative NRT testing during cochlear implantation can be performed effectively using standard hardware and remote-control software. Especially important during the Covid-19 pandemic, such a procedure can reduce in-person contacts, and limit the number of individuals in the operating room. Remote testing can provide additional flexibility and efficiency in audiologist schedules.

Introduction There is limited data correlating preoperative mobility limitations with clinical outcomes in bariatric patients. This study uses propensity score matching (PSM) to compare 30-day outcomes between patients with preoperative limited mobility (LM) versus patients without (non-LM). Methods Using the 2016-2018 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database, patients undergoing primary laparoscopic sleeve gastrectomy or gastric bypass were identified. Two cohorts were defined using preoperative LM status. To adjust for confounders, 1:1 PSM was performed using 25 preoperative characteristics, and balance was assessed with standardized mean difference. Preoperative patient demographics and postoperative 30-day outcomes were compared in both matched and unmatched cohorts. Results 453,146 patients were identified, of which 6942 (1.47%) were LM and 464,555 were non-LM. 1:1 PSM matched 6624 LM to 6624 non-LM patients with good balance for all covariates. LM had higher rates of unplanned intubation (0.4% vs 0.7%, P < .01), unplanned admission to ICU (1.4% vs 2.5%, P < .01), readmissions (4.1% vs 4.9%, P = .036), unplanned reoperation (1.5% vs 2.0%, P = .02), and 30-day mortality (0.2% vs 0.5%, P = .02). Complications including acute renal failure, intra/postoperative myocardial infarction, venous thrombosis, and pulmonary embolism were not significantly different between the matched groups. Conclusion After adjusting for confounders, patients with preoperative limited mobility have higher rates of intubation, ICU admission, reoperation, readmission, and mortality. Prudent pre-operative candidate selection, counseling, and risk mitigation strategies are needed when a patient with limited mobility status is being considered for bariatric surgery.

Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Laparoscopic sleeve gastrectomy (LSG) has demonstrated excellent short-term outcomes. However, existing studies suffer from loss to follow-up, and most long-term data focus on laparoscopic Roux-en-Y gastric bypass (LRYGB). This study compares weight loss in patients ≥5 years from LSG with that in matched patients who underwent LRYGB.The purpose of this study was to compare long-term weight loss in patients undergoing LRYGB and LSG.University hospital, United States.We retrospectively evaluated patients who underwent LSG before August 2012 with follow-up data ≥5 years. LSG patients were matched 1:1 with LRYGB patients by sex, age at surgery, and preoperative body mass index. Univariate and multivariate analyses were performed with weight loss at the longest duration the primary outcome.One-hundred and sixty-five patients underwent LSG during the study period. Long-term follow-up data (≥5 years) were available for 85 patients (52%). There were no preoperative differences between those with and without follow-up data. Six LSG patients (7%) were excluded because they underwent reoperation that altered intestinal anatomy. Of the 79 patients remaining, 75 were matched with post-LRYGB patients. The average follow-up period was 6.4 years for LSG patients and 6.5 years for LRYGB patients (P = .08, not significant). Change in body mass index was 6.81 kg/mLSG is now the most common bariatric surgery in the United States. Long-term data are needed to confirm that observed short-term favorable outcomes are maintained. Recent studies have produced divergent results. We observed significantly less weight loss at ≥5 years in LSG patients compared with matched LRYGB patients.

The shift from fee-for-service to value-based care has focused payers and providers on resource utilization. One important component of value-based care is to reduce the use of post-discharge (PD) services in a clinically appropriate manner following total joint arthroplasty (TJA). Demand matching in healthcare is the process of tailoring appropriate medical care to a patient with respect to that patient's specific medical needs and social determinants. Outcomes following the implementation of a demand-matching algorithm for coordinating PD services after TJA were analyzed in this study.Payment data from all Medicare patients undergoing primary unilateral TJA between July 2014 and December 2018 from a single orthopedic practice were included. These payments were separated into acute and PD care. The initial acute and PD costs were compared to costs at the end of the 4-year study period using multiple linear regression and chi-square.A total of 9,638 patients (4,212 total hip arthroplasties and 5,430 total knee arthroplasties) were included. Acute costs of TJA were stable averaging $13,712.00. PD costs fell steadily from a baseline average of $7,319.00 in July 2014 to $4,678.00 in December 2018 (P.001), representing a 36.1% decline. Discharge to home increased steadily from 45.8% to 79.9% during the same interval (P.001.) CONCLUSION: Our results demonstrate a statistically significant reduction in PD costs over a 4-year period using a demand-matching strategy to align with the Centers for Medicare and Medicaid Services mandate for value-based care. Based on these data, we conclude that thoughtful preoperative assessment of patient factors such as social determinants and medical comorbidities could allow for cost reduction through better utilization of PD services.

An entrustable professional activity (EPA) model was used to assess the anesthesia and surgery competence of year 4 students during elective neutering procedures over 3 academic years (cohort A, cohort B, and cohort C). Two competence thresholds were defined by an expert panel, the minimum acceptable standard (MAS) and the standard expected at the start of final-year rotations (SFR). The assessment scheme performed as expected, and the median level of supervision achieved by students either matched or exceeded the SFR for all EPAs except one, which matched the MAS. Semester of assessment was associated with student performance, with more students in semester 2 achieving the SFR. In the EPAs assessing pain management, documentation, and patient discharge, cohort A was associated with reduced student performance; this could be explained by changes in the delivery of teaching that enhanced performance in subsequent cohorts (academic years). For all EPAs combined and for EPAs 3, 5, 6, 8, and 9, student performance at the SFR was associated with academic year. For all EPAs combined and EPAs 3, 8, and 9, there was a reduction in the proportion of students achieving the SFR threshold in each successive year. At the MAS, the only association for all EPAs combined was with cohort C. This progressive reduction in performance may have been related to the negative effect of decreased time spent at the neutering clinic and loss of feedback opportunities outweighing the positive effects of increased staff:student ratio and improvements in the preparative phases.

Background: Among all patients with cancer, those with advanced non–small cell lung cancer (NSCLC) experience the most distress. Although new therapies are improving survival, it is unknown whether receiving immunotherapy or targeted therapy during the COVID-19 pandemic increases patients’ psychological vulnerability. To meet clinical needs, knowledge of patients’ COVID-19 perceptions and safety behaviors is essential. Thus, this study compared patients’ psychological responses at diagnosis and during COVID-19 and compared patients with similar individuals without cancer during the same period. Patients and Methods: Patients with advanced NSCLC enrolled at diagnosis for cohort study participated (ClinicalTrials.gov identifier: NCT03199651). Those with follow-ups from April 28, 2020, through July 14, 2020 (n=76), were assessed again including COVID-19 measures. Simultaneously, community controls with similar sociodemographics and smoking histories were solicited (n=67). Measures were COVID-19 perceptions (Brief Illness Perception Questionnaire), social distancing, and depressive (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7) symptoms. First, analyses evaluated differences in the psychological responses of patients with NSCLC at diagnosis and during COVID-19. Second, patients and controls were contrasted on COVID-19 perceptions, social distancing, and psychological symptoms. Results: The depressive and anxious symptoms of patients with NSCLC were greater at diagnosis (PPP>.406). Notably, controls anticipated the COVID threat would last longer, practiced more social distancing, were more concerned about family (P<.04), and reported worse psychological symptoms (PConclusions: Despite multiple health stressors, patients with NSCLC demonstrated resilience when receiving cancer treatment during COVID-19. Nonetheless, this population remains psychologically vulnerable, requiring support at diagnosis and thereafter.

Scholars in the field of community psychology have called for more research dedicated to examining White privilege as part of a system of White supremacy in the United States. One branch of this work focuses on awareness of White privilege, yet to date, this research has typically investigated awareness of White privilege at individual levels of analysis instead of also focusing on neighborhoods, schools, and other levels of analysis beyond the individual. In this study, we combine survey and U.S. Census data to explore both individual- and community-level predictors of White privilege awareness. With a sample of 1285 White college students, we found that gender, modern racism, social dominance orientation, and subjective socioeconomic status (SES) significantly predicted White privilege awareness. After accounting for these individual-level variables, we found that characteristics of students' hometowns (defined by zip code) predicted White privilege awareness. Specifically, greater income inequality was associated with higher White privilege awareness, while greater White racial homogeneity was marginally associated with lower White privilege awareness. There was a significant interaction between community-level White racial homogeneity and individual-level subjective SES, such that students with high subjective SES and low White racial homogeneity had the highest White privilege awareness. This study highlights the importance of examining different facets of ecological context in relation to White Americans' racial attitudes.

Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high-resolution fluid-attenuated inversion recovery (FLAIR)-DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR-DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

Background Malnutrition among children under five years of age is a major public health issue in many low and middle-income constrained countries. According to WHO, 5.3 million under-five children die every year and about 45% of these deaths are linked to malnutrition. While it is clear that poverty and lack of food are important factors in children’s malnutrition, less is known about the ways in which local conceptions of malnutrition affect parents’ treatment choices. In Ethiopia, child malnutrition is a severe public health problem and a common cause of child death, and this paper explores the local views of malnutrition and how these shape people’s health-seeking behaviour. Methods The study was conducted in eastern Ethiopia from December 2017 to January 2019, conducting interviews and focus group discussions to explore different views and treatment options malnutrition. The study used grounded theory because it allows new and unexpected themes to arise from the data. Researchers’ assumptions on local terminologies of child malnutrition are also controlled as a principle of ground theory. Results Child malnutrition was not only perceived to be related to lack of food but was understood in a wider local conceptualization of health and illness. Parents often relied on healers because they are long-standing members of the community, possess indigenous knowledge, and cost less than other options. Because health professionals and the community perceive and speak of health very differently, people often do not seek support from health services. The misalignments between how health professionals and healers diagnose and treat malnourished children have implications on the possibilities to implement change to reduce malnutrition. Conclusions Through an exploration of people’s own terminology and understandings of what a malnourished child is, as well as the underlying reasons for their illness, this paper explores how people understand malnutrition symptoms and why many tend to rely on healers rather than seeking care from health centres.

Objective: Sporadic Creutzfeldt–Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI). Methods: MRI of 1,458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile for each MRI scan. We selected 487 patients with autopsy-confirmed diagnosis of “pure” sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data-driven procedures for subtype diagnosis: the first procedure—prion subtype classification algorithm with MRI (PriSCA_MRI)—uses only MRI examinations; the second—PriSCA_MRI + Gen—includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on the first MRI and the last MRI follow-up. Results: PriSCA_MRI classified the 3 most prevalent subtypes with 82% accuracy. PriSCA_MRI + Gen raised the accuracy to 89% and identified all subtypes. Individually, the 2 most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with sensitivities up to 95 and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. Interpretation: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. ANN NEUROL 2021;89:560–572.

To determine whether final year veterinary students take longer to perform endotracheal intubation than qualified veterinary surgeons.Observational cohort study.A total of 38 healthy mesocephalic dogs undergoing general anaesthesia for a clinical purpose unrelated to this study.Time to successful endotracheal intubation, measured from termination of intravenous induction drug administration to confirmation of endotracheal intubation, was recorded for two groups: final year veterinary students (group S) and qualified veterinary surgeons (group V). Animal age, breed and anaesthetic induction agent were also recorded. Following normality testing the groups were compared for each variable using the Student's t test or Mann-Whitney U test where appropriate. The level of significance was defined as p0.05. Timed data are presented as median and interquartile range.Time to successful intubation was 54.2 (31.3) seconds in group S and 11.7 (8.5) seconds in group V, the difference being significant (p0.001). There was also a significant difference between groups for animal age (p = 0.036) but not for breed (p = 0.573) or induction agent (p = 0.239).and clinical relevance Veterinary students take longer to achieve successful endotracheal intubation of anaesthetized healthy dogs compared with qualified veterinary surgeons. To mitigate any additional risk of dogs developing hypoxaemia, it is recommended that a 55 second time limit is set after which the supervisor intervenes and takes over the intubation procedure. Preoxygenation may be used as an additional mitigation strategy.

Background Obesity and comorbid conditions are associated with worse outcomes related to COVID-19. Moreover, social distancing adherence during the COVID-19 pandemic may predict weight gain due to decreased physical activity, increased emotional eating, and social isolation. While early studies suggest that many individuals struggled with weight management during the pandemic, less is known about healthy eating and weight control behaviors among those enrolled in weight loss programs. Methods The present study evaluated weight management efforts among weight loss program participants during the COVID-19 pandemic. Participants’ (N = 55, 90.9% female, 36% white, Mage = 49.8) demographics and body mass index were collected two months prior to the COVID-19 statewide shutdown. During the lockdown, an online survey assessed health behaviors, coping, COVID-19 experiences (e.g., social distancing, loneliness), and weight gain. Logistic regressions examined demographics, health behaviors, and COVID-19 factors as predictors of weight gain. Results Most participants (58%) reported gaining weight during COVID-19. Weight gain was predicted by challenges with the following health behaviors: physical activity, monitoring food intake, choosing healthy foods, and emotional eating. Loneliness and working remotely significantly related to emotional eating, physical activity, and choosing healthy foods. Conclusions Loneliness and working remotely increased the difficulty of weight management behaviors during COVID-19 among weight loss program participants. However, staying active, planning and tracking food consumption, choosing healthy foods, and reducing emotional eating protected against weight gain. Thus, these factors may be key areas for weight management efforts during the pandemic.

Perioperative management for patients undergoing shoulder arthroplasty has evolved significantly over the years to reduce overt complications and improve patient outcomes. The groundwork for perioperative care encompasses initial patient selection and education strategies for achieving successful outcome. Multimodal pain management strategies have advanced patient care with the increased use of new regional/local anesthetics. In addition, complications resulting from blood loss and transfusions have been curtailed with the use of synthetic antifibrinolytic agents. It remains critical for shoulder arthroplasty surgeons to optimize patients during the perioperative period through various modalities to maximize functional progression, outcomes, and patient's satisfaction following shoulder arthroplasty.

Immunoglobulin light chain (AL) amyloidosis is an incurable hematologic disorder typically characterized by the production of amyloidogenic light chains by clonal plasma cells. These light chains misfold and aggregate in healthy tissues as amyloid fibrils, leading to life-threatening multi-organ dysfunction. Here we show that the clonal plasma cells in AL amyloidosis are highly primed to undergo apoptosis and dependent on pro-survival proteins MCL-1 and BCL-2. Notably, this MCL-1 dependency is indirectly targeted by the proteasome inhibitor bortezomib, currently the standard of care for this disease and the related plasma cell disorder multiple myeloma, due to upregulation of pro-apoptotic Noxa and its inhibitory binding to MCL-1. BCL-2 inhibitors sensitize clonal plasma cells to multiple front-line therapies including bortezomib, dexamethasone and lenalidomide. Strikingly, in mice bearing AL amyloidosis cell line xenografts, single agent treatment with the BCL-2 inhibitor ABT-199 (venetoclax) produces deeper remissions than bortezomib and triples median survival. Mass spectrometry-based proteomic analysis reveals rewiring of signaling pathways regulating apoptosis, proliferation and mitochondrial metabolism between isogenic AL amyloidosis and multiple myeloma cells that divergently alter their sensitivity to therapies. These findings provide a roadmap for the use of BH3 mimetics to exploit endogenous and induced apoptotic vulnerabilities in AL amyloidosis.

Background There is a paucity of data on the outcomes of distal femoral replacements (DFRs) in patients with total knee arthroplasty (TKA) periprosthetic fractures. We sought to characterize these patients’ survivorship free from rerevision. Methods We retrospectively identified 49 patients, including 34 after primary TKA (primary cohort), 9 after revision TKA, and 6 conversions for failed open reduction and internal fixation (revision cohort) that underwent DFR for a periprosthetic femur fracture. The mean age was 76 years, and 40 patients (82%) were female. The mean follow-up was 4 years. Femoral fixation included 44 cemented stems (90%) and 5 cementless stems (10%). Survivorship free from rerevision was characterized by the Kaplan–Meier method; cox proportional regression was used to analyze the risk factors for rerevision. Results Survivorship free from any rerevision at 5 years in the primary and revision cohort was 93% and 18%, respectively. The revision cohort had a 5.3× higher risk of re-revision (P = .008). Survivorship free from re-revision for aseptic loosening at 5 years in the primary and revision cohort was 93% and 53%, respectively. Two of the 3 patients with cementless stems in the primary cohort underwent early rerevision for aseptic loosening, but patients with prior primary TKAs treated with cemented femoral fixation (n = 31) had a 97% 5-year survivorship free from re-revision. Conclusion Patients with periprosthetic fractures around prior primary TKAs treated with DFRs with cemented femoral fixation had a 97% 5-year survivorship free from any re-revision. DFRs for periprosthetic femur fractures around revision TKAs or conversions of failed open reduction and internal fixations have a 5× increased risk of rerevision.

Four cases of oseltamivir-resistant influenza A(H1N1)pdm09 virus infection were detected among inhabitants of a border detention center in Texas, USA. Hemagglutinin of these viruses belongs to 6B.1A5A-156K subclade, which may enable viral escape from preexisting immunity. Our finding highlights the necessity to monitor both drug resistance and antigenic drift of circulating viruses.

Objective Among patients with type 2 diabetes (T2D), the prevalence of hidden hypercortisolism (HidHyCo, formally called subclinical hypercortisolism or mild autonomous cortisol secretion) was estimated to be 2.2-12.1%. The aim of this study was to investigate whether the available literature helps to identify the characteristics of T2D patients more frequently associated with HidHyCo. Methods A meta-analysis was performed using studies that assessed both the prevalence of HidHyCo in patients with T2D and the characteristics of these patients with and without HidHyCo. The DerSimonian and Laird (DSL) and the Hartung, Knapp, Sidik and Jonkman (HKSJ) methods were utilized. Results Among the 18 available studies, 6 studies provided the necessary data. The association between HidHyCo and advanced T2D (based on the patients’ description given in each study in presence of micro/ microvascular complications, or insulin treatment plus hypertension, or hypertension treated with ≥2 drugs), hypertension, insulin treatment and dyslipidemia was reported in 5 (2184 patients), 6 (2283 patients), 3 (1440 patients), and 3 (987 patients) studies, respectively. HidHyCo was associated with advanced T2D as assessed with both DSL (odds ratio, OR, 3.47, 95% Confidence Interval, 95%CI, 2.12-5.67) and HKSJ method (OR 3.60, 95%CI 2.03-6.41) and with the prevalence of hypertension or of insulin treatment as assessed by the DSL approach (OR 1.92, 95%CI 1.05-3.50 and OR 2.29, 95%CI 1.07-4.91, respectively), but not as assessed with HKSJ method. Conclusions Patients with advanced T2D have a higher prevalence of HidHyCo. These data inform about the selection of T2D patients for HidHyCo screening.

MYL-1601D is a proposed biosimilar of originator insulin aspart, NovologThis study assessed the immunogenicity, efficacy, and safety of MYL-1601D with Ref-InsAsp-US in patients with type 1 diabetes mellitus (T1D).This was a 24-week, open-label, randomized, phase III study. Patients were randomized 1:1 to mealtime MYL-1601D or Ref-InsAsp-US in combination with insulin glargine (Lantus SoloSTARIn total, 478 patients were included in the intent-to-treat analysis (MYL-1601D: 238; Ref-InsAsp-US: 240) set. The 90% confidence interval (CI) for the primary endpoint was within the pre-defined equivalence margin of ±11.7% and the treatment differences (SE) in TEAR responders between the treatment groups was - 2.86 (4.16) with 90% CI - 9.71 to 3.99. The mean (SD) changes from baseline for HbA1c, FPG, and insulin dosages were similar in both groups at week 24. The safety profiles including hypoglycemia, immune-related events, AEs, and other reported variables were similar between the treatment groups at week 24.MYL-1601D demonstrated similar immunogenicity, efficacy, and safety profiles to Ref-InsAsp-US in patients with T1D over 24 weeks. CLINICAL TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03760068.

This multicenter study aimed to evaluate the auditory and speech outcomes of cochlear implantation (CI) in deaf-blind patients compared with deaf-only patients.Retrospective cohort study.Multiple cochlear implant centers.The current study was conducted on 17 prelingual deaf-blind children and 12 postlingual deaf-blind adults who underwent CI surgery. As a control group, 17 prelingual deaf children and 12 postlingual deaf adults were selected.Cochlear implantation.Auditory and linguistic performances in children were assessed using the categories of auditory performance (CAP) and Speech Intelligibility Rating (SIR) scales, respectively. The word recognition score (WRS) was also used to measure speech perception ability in adults. The mean CAP, SIR, and WRS cores were compared between the deaf-only and deaf-blind groups before CI surgery and at "12 months" and "24 months" after device activation. Cohen's d was used for effect size estimation.We found no significant differences in the mean CAP and SIR scores between the deaf-blind and deaf-only children before the CI surgery. For both groups, SIR and CAP scores improved with increasing time after the device activation. The mean CAP scores in the deaf-only children were either equivalent or slightly higher than those of the deaf-blind children at "12 months post-CI" (3.94 ± 0.74 vs 3.24 ± 1.25; mean difference score, 0.706) and "24 months post-CI" (6.01 ± 0.79 vs 5.47 ± 1.06; mean difference score, 0.529) time intervals, but these differences were not statistically significant. The SIR scores in deaf-only implanted children were, on average, 0.870 scores greater than the deaf-blind children at "12 months post-CI" (2.94 ± 0.55 vs 2.07 ± 1.4; p = 0.01, d = 0.97) and, on average, 1.067 scores greater than deaf-blind children at "24 months post-CI" (4.35 ± 0.49 vs 3.29 ± 1.20; p = 0.002; d = 1.15) time intervals. We also found an improvement in WRS scores from the "preimplantation" to the "12-month post-CI" and "24-month post-CI" time intervals in both groups. Pairwise comparisons indicated that the mean WRS in the deaf-only adults was, on average, 10.61% better than deaf-blind implanted adults at "12 months post-CI" (62.33 ± 9.09% vs 51.71 ± 10.73%, p = 0.034, d = 1.06) and, on average, 15.81% better than deaf-blind adults at "24-months post-CI" (72.67 ± 8.66% vs 56.8 ± 9.78%, p = 0.002, d = 1.61) follow-ups.Cochlear implantation is a beneficial method for the rehabilitation of deaf-blind patients. Both deaf-blind and deaf-only implanted children revealed similar auditory performances. However, speech perception ability in deaf-blind patients was slightly lower than the deaf-only patients in both children and adults.

Ecological momentary assessment (EMA) studies have provided conflicting evidence for the mood regulation tenet that people drink in response to positive and negative moods. The current study examined mood-to-alcohol relationships idiographically to quantify the prevalence and intensity of relationships between positive and negative moods and drinking across individuals.We used two EMA samples: 96 heavy drinking college students (sample 1) and 19 young adults completing an ecological momentary intervention (EMI) for drinking to cope (sample 2). Mood and alcohol use were measured multiple times per day for 4-6 weeks. Mood-alcohol relationships were examined using three different analytic approaches: standard multilevel modeling, group causal modeling, and idiographic causal modeling.Both multilevel modeling and group causal modeling showed that participants in both samples drank in response to positive moods only. However, idiographic causal analyses revealed that only 63% and 21% of subjects (in samples 1 and 2, respectively) drank following any positive mood. Many subjects (24% and 58%) did not drink in response to either positive or negative mood in their daily lives, and very few (5% and 16%) drank in response to negative moods throughout the EMA protocol, despite sample 2 being selected specifically because they endorse drinking to cope with negative mood.Traditional group-level analyses and corresponding population-wide theories assume relative homogeneity within populations in mood-alcohol relationships, but this nomothetic approach failed to characterize accurately the relationship between mood and alcohol use in approximately half of the subjects in two samples that were demographically and clinically homogeneous. Given inconsistent findings in the mood-alcohol relationships to date, we conclude that idiographic causal analyses can provide a foundation for more accurate theories of mood and alcohol use. In addition, idiographic causal models may also help improve psychosocial treatments through direct use in clinical settings.

Cannabis is well established as possessing immune modulating activity. The objective of this study was to evaluate the anti-inflammatory properties of selected cannabis-derived terpenes and cannabinoids. Based on their activity in cannabis-chemovar studies, α-pinene, trans-nerolidol, D-limonene, linalool and phytol were the selected terpenes evaluated. The cannabinoid compounds evaluated included cannabidivarin, cannabidiol, cannabinol, cannabichromene, cannabigerol and delta-9-tetrahydrocannabinol. Human PBMC were pretreated with each compound, individually, at concentrations extending from 0.001 to 10 μM and then stimulated with CpG (plasmacytoid dendritic cell), LPS (monocytes), or anti-CD3/CD28 (T cells). Proliferation, activation marker expression, cytokine production and phagocytosis, were quantified. Of the 21 responses assayed for each compound, cannabinoids showed the greatest immune modulating activity compared to their vehicle control. Delta-9-tetrahydrocannabinol possessed the greatest activity affecting 11 immune parameters followed by cannabidivarin, cannabigerol, cannabichromene, cannabinol and cannabidiol. α-Pinene showed the greatest immune modulating activity from the selected group of terpenes, followed by linalool, phytol, trans-nerolidol. Limonene had no effect on any of the parameters tested. Overall, these studies suggest that selected cannabis-derived terpenes displayed minimal immunological activity, while cannabinoids exhibited a broader range of activity. Compounds possessing anti-inflammatory effects may be useful in decreasing inflammation associated with a range of disorders, including neurodegenerative disorders.

This is a single-center randomized open label active-controlled crossover trial comparing efficacy and safety of fast acting insulin aspart (FA) (FIASP®) versus insulin aspart (IAsp) (NovoLog®) when used in the Medtronic 670G system in auto mode in patients with type 1 diabetes. Forty patients were randomized to either IAsp or FA. Each treatment period was 7 weeks and a standardized meal test was administered 6 weeks after the start of each treatment period. The primary endpoint was postprandial glucose (PPG) increment after the meal test at 1 h. Treatment with FA using the MiniMed 670G hybrid closed loop (HCL) led to a greater reduction in 1-h postprandial glucose increase compared with treatment with IAsp during the standardized mixed meal test. Change in glucose: [estimated treatment difference (ETD ± standard deviation [SD]); 95% confidence interval]: 70.27 (±17.36) mg/dL (3.9 ± 1.0 mmol/L) with FA versus 98.42 (±17.36) mg/dL (5.5 ± 1.0 mmol/L) with IAsp (P = 0.008). Patients spent 1.81% (P = 0.016) more time (equivalent to 26 min per day) in the 70–180 mg/dL (3.89–9.99 mmol/L) range with FA than with IAsp. The entire sample spent only 0.5% of time

Thousand and one amino‐acid kinase 1 (TAOK1) is a MAP3K protein kinase, regulating different mitogen‐activated protein kinase pathways, thereby modulating a multitude of processes in the cell. Given the recent finding of TAOK1 involvement in neurodevelopmental disorders (NDDs), we investigated the role of TAOK1 in neuronal function and collected a cohort of 23 individuals with mostly de novo variants in TAOK1 to further define the associated NDD. Here, we provide evidence for an important role for TAOK1 in neuronal function, showing that altered TAOK1 expression levels in the embryonic mouse brain affect neural migration in vivo, as well as neuronal maturation in vitro. The molecular spectrum of the identified TAOK1 variants comprises largely truncating and nonsense variants, but also missense variants, for which we provide evidence that they can have a loss of function or dominant‐negative effect on TAOK1, expanding the potential underlying causative mechanisms resulting in NDD. Taken together, our data indicate that TAOK1 activity needs to be properly controlled for normal neuronal function and that TAOK1 dysregulation leads to a neurodevelopmental disorder mainly comprising similar facial features, developmental delay/intellectual disability and/or variable learning or behavioral problems, muscular hypotonia, infant feeding difficulties, and growth problems., In this study we expand the cohort of individuals with a neurodevelopmental disorder, carrying a de novo variant in TAOK1 (a), thereby further defining the neurodevelopmental disorder caused by TAOK1 malfunctioning. Using both in vivo (b) and in vitro (c) functional assays, we provide evidence that increased as well as decreased levels of TAOK1 cause disruption of neuronal development, showing that TAOK1 plays an important role in neuronal function. Additionally, our data suggests that both gain of function as well as loss of function mutations are potentially causative for the TAOK1‐related neurodevelopmental disorder.