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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.

To report clinical and patient-reported outcome measures (PROMs) in patients undergoing revision surgery after diagnosis of anchor-induced arthropathy.Patients who underwent revision arthroscopic shoulder surgery and were diagnosed with post-instability glenohumeral arthropathy performed from January 2006 to May 2018 were included in the current study. Patients were excluded if they underwent prior open shoulder procedures, if glenoid bone loss was present, or if prerevision imaging and records were incomplete or not available. Data included initial diagnosis and index procedure performed, presenting arthropathy symptoms including duration, exam findings before revision surgery, and surgical intervention. PROMs were prospectively collected before surgery and at minimum 2-year follow-up.Fourteen patients were included with a mean (± standard deviation) age at presentation of 35.2 ± 12.1 years (range 16 to 59). The follow-up rate was 86%, with a mean follow-up of 3.8 years (range 1.1 to 10.6). Mean time to development of arthropathy symptoms was 48.2 months (range1 month to 13.8 years), all presenting with pain and decreased range of motion on exam. At time of revision surgery, all patients underwent either open or arthroscopic removal of previous implants, including anchors and suture material. Six patients underwent additional revision stabilization procedures, 1 underwent total shoulder arthroplasty, and 7 underwent arthroscopic intraarticular debridement, capsular release, and chondroplasty with or without microfracture. Pain significantly improved in 79% of patients (P = .05). Significant improvements in all PROMs were observed, including 12-item Short Form (43.8 to 54.8, P.01); Disabilities of the Arm, Shoulder, and Hand, shortened version (31.8 to 8.4, P.01); Single Assessment Numeric Evaluation (47.0 to 84.5, P.05); and American Shoulder and Elbow Surgeons (61.6 to 92.1, P.01). Average external rotation significantly improved, from 31° ± 22° to 52° ± 24° (P = .02).Rapid intervention after diagnosis, through either revision arthroscopic or open debridement and stabilization, can lead to significant improvement in range of motion, pain, and overall patient function and satisfaction.IV, retrospective case series.

The purpose of this study was to investigate the role of preoperative bone marrow lesion (BML) size and location on (1) postoperative patient reported outcomes and (2) postoperative failure and time to failure after osteochondral allograft (OCA) transplantation.Consecutive patients from 2 senior surgeons who underwent isolated OCA transplantation to the knee from 2009-2018 were identified for the case series. Preoperative magnetic resonance imaging (MRI) was evaluated for BMLs based on 2 classification systems (Welsch et al. and Costa-Paz et al.) by 2 independent graders. BMLs associated with minimum 1-year postoperative outcomes were evaluated, and the effect of BML classification on survivorship was investigated with Kaplan-Meier curves.The 77 patients who underwent isolated OCA transplantation (mean follow-up: 39.46 ± 22.67 months) and had preoperative MRIs were included. Within this cohort, 82% of patients demonstrated a BML. The preoperative Costa-Paz et al. classification was significantly positively correlated with the postoperative Visual Analog Scale, International Knee Documentation Committee and Veterans RAND 12-Item Health Survey raw scores for both graders (P0.05). Failure occurred in 5 of 65 (8%) patients at a mean of 22.86 ± 12.04 months postoperatively. The presence of BML alone did not significantly affect survival (P = 0.780). However, for 1 grader, the Welsch et al. classification was associated with increased risk of graft failure (P = 0.031).Preoperative subchondral BMLs were present in 82% of patients undergoing OCA transplantation. We found that more severe BMLs based on the Costa-Paz classification, with increasing involvement in the juxta-articular surface, were correlated with higher postoperative patient-reported functional outcomes after OCA. BMLs may be associated with an increase in graft failure, but their role in this remains unclear.IV, Retrospective Case Series.

BACKGROUND AND OBJECTIVE: Folate and vitamin B12 deficiencies can impair proper growth and brain development in children. Data on the folate and vitamin B12 status of children aged 6–59 months in Guatemala are scarce. Identification of factors associated with higher prevalence of these micronutrient deficiencies within the population is needed for national and regional policymakers. OBJECTIVE: To describe national and regional post-fortification folate and vitamin B12 status of children aged 6–59 months in Guatemala. METHODS: A multistage, cluster probability study was carried out with national and regional representation of children aged 6–59 months. Demographic and health information was collected for 1246 preschool children, but blood samples for red blood cell (RBC) folate and vitamin B12 were collected and analyzed for 1,245 and 1143 preschool children, respectively. We used the following deficiency criteria as cutoff points for the analyses: < 305 nmol/L for RBC folate, < 148 pmol/L for vitamin B12 deficiency, and 148–221 pmol/L for marginal vitamin B12 deficiency. Prevalence of RBC folate deficiency and vitamin B12 deficiency and marginal deficiency were estimated. Prevalence risk ratios of RBC folate and vitamin B12 deficiency were estimated comparing subpopulations of interest. RESULTS: The national prevalence estimates of RBC folate deficiency among children was 33.5% [95% CI 29.1, 38.3]. The prevalence of RBC folate deficiency showed wide variation by age (20.3–46.6%) and was significantly higher among children 6–11 months and 12–23 months (46.6 and 37.0%, respectively), compared to older children aged 48–59 months (20.3%). RBC folate deficiency also varied widely by household wealth index (22.6–42.0%) and geographic region (27.2–46.7%) though the differences were not statistically significant. The national geometric mean for RBC folate concentrations was 354.2 nmol/L. The national prevalences of vitamin B12 deficiency and marginal deficiency among children were 22.5% [95% CI 18.2, 27.5] and 27.5% [95% CI 23.7, 31.7], respectively. The prevalence of vitamin B12 deficiency was significantly higher among indigenous children than among non-indigenous children (34.5% vs. 13.1%, aPRR 2.1 95% CI 1.4, 3.0). The prevalence of vitamin B12 deficiency also significantly varied between the highest and lowest household wealth index (34.3 and 6.0%, respectively). The national geometric mean for vitamin B12 concentrations was 235.1 pmol/L. The geometric means of folate and B12 concentrations were significantly lower among children who were younger, had a lower household wealth index, and were indigenous (for vitamin B12 only). Folate and vitamin B12 concentrations showed wide variation by region (not statistically significant), and the Petén and Norte regions showed the lowest RBC folate and vitamin B12 concentrations, respectively. CONCLUSIONS: In this study, a third of all children had RBC folate deficiency and half were vitamin B12 deficient. Folate deficiency was more common in younger children and vitamin B12 deficiency was more common in indigenous children and those from the poorest families. These findings suggest gaps in the coverage of fortification and the need for additional implementation strategies to address these gaps in coverage to help safeguard the health of Guatemalan children.

Increased physical activity has shown positive effects on various hippocampal memory functions through accumulating evidence that physical exercise and higher cardiorespiratory fitness can enhance human performance on nonspatial mnemonic discrimination tasks that rely on hippocampal pattern separation. However, there is less direct evidence of exercise effects on spatial pattern separation in humans, despite evidence for this association in rodent models. We examined the influence of strenuous exercise habits on spatial mnemonic discrimination among 176 young adults. We used a delayed match-/non-match-to-sample (same/different) task to assess pattern separation for spatial locations across varying degrees of similarity. Participants who reported regularly engaging in strenuous exercise three or more times per week performed significantly better than those who reported engaging in strenuous exercise fewer than three times per week, even when pattern separation tasks involved higher spatial similarity. These apparent exercise effects were observed for female, but not male, participants. These findings support likely benefits of strenuous exercise habits for human spatial pattern separation skills, and they suggest a need to explore potential interaction effects of exercise and gender.

Introduction: Voters facing illness or disability are disproportionately under-represented in terms of voter turnout. Earlier research has indicated that enfranchisement of these populations may reinforce the implementation of policies improving health outcomes and equity. Due to the confluence of the coronavirus 2019 (COVID-19) pandemic and the 2020 election, we aimed to assess emergency absentee voting processes, which allow voters hospitalized after regular absentee deadlines to still obtain an absentee ballot, and election changes due to COVID-19 in all 50 states. Methods: We performed a cross-sectional study collecting 34 variables pertaining to emergency voting processes and COVID-19-related election changes, including deadlines, methods of submission for applications and ballots, and specialized services for patients. Data were obtained from, in order of priority, state boards of elections websites, poll worker manuals, application forms, and state legislation. We verified all data through direct correspondence with state boards of elections. Results: Emergency absentee voting processes are in place in 39 states, with the remaining states having universal vote-by-mail (n = 5) or extended regular absentee voting deadlines (n = 6). The emergency absentee period most commonly began within 24 hours following the normal absentee application deadline, which was often seven days before an election (n = 11). Unique aspects of emergency voting processes included patients designating an “authorized agent” to deliver their applications and ballots (n = 38), electronic ballot delivery (n = 5), and in-person teams that deliver ballots directly to patients (n = 18). Documented barriers in these processes nationwide include unavailable online information (n = 11), restrictions mandating agents to be family members (n = 7), physician affidavits or signatures (n = 9), and notary or witness signature requirements (n = 15). For the November 2020 presidential election, 12 states expanded absentee eligibility to allow COVID-19 as a reason to request an absentee ballot, and 18 states mailed absentee ballot applications or absentee ballots to all registered voters. Conclusion: While 39 states operate emergency absentee voting processes for hospitalized voters, there are considerable areas for improvement and heterogeneity in guidelines for these protocols. For future election cycles, information on emergency voting and broader election reforms due to COVID-19 may be useful for emergency providers and patients alike to improve the democratic participation of voters experiencing illness. [ABSTRACT FROM AUTHOR] Copyright of Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health is the property of Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the beginning of the COVID-19 pandemic, there were major concerns regarding the huge demand for asthma inhalers. Using the primary-care medical records for 614,700 asthma patients between January and June 2020, we found that there was a substantial increase in inhalers solely in March 2020. Patients significantly associated with receiving higher inhaled corticosteroid prescriptions were younger, of higher socioeconomic status, and had milder asthma.

The hip capsule and acetabular labrum are critical structures that function to protect and stabilize the hip joint. As the use of hip arthroscopy increases, there is increasing interest in the integrity of the hip capsule and labrum in optimizing postoperative function and outcomes. In this report, we describe the surgical technique for capsular reconstruction with dermal allograft and labral augmentation with tibialis anterior allograft for the treatment of gross instability after hip arthroscopy. This technique may be applied in situations with large capsular defects and deficient labral tissue., Technique Video Video 1 Intraoperative assessment of the central compartment revealed labral insufficiency with residual femoroacetabular impingement syndrome pathology. Viewing from the MMAP, the first suture anchor is placed at the 10-o’clock position via the AL portal. The suture from the suture anchor is used to measure the length of labral insufficiency, which was 4.2 cm. The remaining 3 suture anchors are placed up to the 4-o’clock position through the DALA portal. Two double-loaded suture anchors are placed adjacent to the head of the rectus femoris tendon along the acetabulum for capsular reconstruction. The labral allograft is passed through the DALA portal using the Kite technique and knotted down anteromedially to posterolaterally. Upon plication of the vertical limb of the capsulotomy, a 2.0 × 2.5-cm defect remained. Sutures from the double-loaded anchors are passed through the distal lateral and distal medial T-capsulotomy leaflets in a mattress fashion and knotted. One suture from the proximal anchor and one suture from the distal anchor is retrieved through the DALA portal and passed through the proximal and distal corners of the capsular allograft, respectively. The graft is then shuttled through the DALA portal using the Kite technique and each corner is knotted down in a simple fashion. A dynamic examination is then performed to evaluate graft placement. (AL, anterolateral; DALA, distal anterior lateral accessory; MMAP, modified mid-anterior portal.)

Introduction: This study reviews malpractice, also called medical professional liability (MPL), claims involving adult patients cared for in emergency departments (ED) and urgent care settings. Methods: We conducted a retrospective review of closed MPL claims of adults over 18 years, from the Medical Professional Liability Association’s Data Sharing Project database from 2001–2015, identifying 6,779 closed claims. Data included the total amount, origin, top medical specialties named, chief medical factors, top medical conditions, severity of injury, resolution, average indemnity, and defense costs of closed claims. Results: Of 6,779 closed claims, 65.9% were dropped, withdrawn, or dismissed. Another 22.8% of claims settled for an average indemnity of $297,709. Of the 515 (7.6%) cases that went to trial, juries returned verdicts for the defendant in 92.6% of cases (477/515). The remaining 7.4% of cases (38/515) were jury verdicts for the plaintiff, with an average indemnity of $816,909. The most common resulting medical condition cited in paid claims was cardiac or cardiorespiratory arrest (10.4%). Error in diagnosis was the most common chief medical error cited in closed claims. Death was the most common level of severity listed in closed (38.5%) and paid (42.8%) claims. Claims reporting major permanent injury had the highest paid-to-closed ratio, and those reporting grave injury had the highest average indemnity of $686,239. Conclusion: This retrospective review updates the body of knowledge surrounding medical professional liability and represents the most recent analysis of claims in emergency medicine. As the majority of emergency providers will be named in a MPL claim during their career, it is essential to have a better understanding of the most common factors resulting in MPL claims.

As college campuses reopen, we are in the midst of a large-scale experiment on the efficacy of various strategies to contain the SARS-CoV-2 virus. Traditional individual surveillance testing via nasal swabs and/or saliva is among the measures that colleges are pursuing to reduce the spread of the virus on campus. Additionally, some colleges are testing wastewater on their campuses for signs of infection, which can provide an early warning signal for campuses to locate COVID-positive individuals. However, a representation of wastewater surveillance has not yet been incorporated into epidemiological models for college campuses, nor has the efficacy of wastewater screening been evaluated relative to traditional individual surveillance testing, within the structure of these models. Here, we implement a new model component for wastewater surveillance within an established epidemiological model for college campuses. We use a hypothetical residential university to evaluate the efficacy of wastewater surveillance to maintain low infection rates. We find that wastewater sampling with a 1-day lag to initiate individual screening tests, plus completing the subsequent tests within a 4-day period can keep overall infections within 5% of the infection rates seen with traditional individual surveillance testing. Our results also indicate that wastewater surveillance can be an effective way to dramatically reduce the number of false positive cases by identifying subpopulations for surveillance testing where infectious individuals are more likely to be found. Through a Monte Carlo risk analysis, we find that surveillance testing that relies solely on wastewater sampling can be fragile against scenarios with high viral reproductive numbers and high rates of infection of campus community members by outside sources. These results point to the practical importance of additional surveillance measures to limit the spread of the virus on campus and the necessity of a proactive response to the initial signs of outbreak.Author SummaryCollege campuses have employed a variety of measures to keep their communities safe amid the SARS-CoV-2 pandemic. Many colleges are implementing surveillance testing programs wherein students are randomly selected to be tested for SARS-CoV-2. These strategies aim to manage the number of infections among the student population by isolating infected individuals. Some colleges are monitoring wastewater on their campuses for signs of the virus, which has been found to be capable of detecting viral RNA. If a wastewater sample shows signs of viral RNA, then screening tests are administered to the individuals who live or work in the buildings that contribute to the sewer in question. We present a model for such wastewater surveillance within a larger model for the spread of SARS-CoV-2 on a college campus. We show that wastewater surveillance can reduce the number of false positive cases and the associated disruptions to student life, while maintaining similar overall numbers of infections. However, we find that surveillance testing strategies that rely solely on wastewater sampling may be less effective if the local transmission rate of the virus is high, or if the rate of infection of members of the campus community by outside sources is high.

BACKGROUND: High diet quality is associated with a lower risk of chronic diseases. Metabolomics can be used to identify objective biomarkers of diet quality. OBJECTIVES: We used metabolomics to identify serum metabolites associated with 4 diet indices and the components within these indices in 2 samples from African Americans and European Americans. METHODS: We studied cross-sectional associations between known metabolites and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension Trial (DASH) diet, alternate Mediterranean diet (aMED), and their components using untargeted metabolomics in 2 samples (n(1) = 1,806, n(2) = 2,056) of the Atherosclerosis Risk in Communities study (aged 45–64 y at baseline). Dietary intakes were assessed using an FFQ. We used multivariable linear regression models to examine associations between diet indices and serum metabolites in each sample, adjusting for participant characteristics. Metabolites significantly associated with diet indices were meta-analyzed across 2 samples. C-statistics were calculated to examine if these candidate biomarkers improved prediction of individuals in the highest compared with lowest quintile of diet scores beyond participant characteristics. RESULTS: Seventeen unique metabolites (HEI: n = 6; AHEI: n = 5; DASH: n = 14; aMED: n = 2) were significantly associated with higher diet scores after Bonferroni correction in sample 1 and sample 2. Six of 17 significant metabolites [glycerate, N-methylproline, stachydrine, threonate, pyridoxate, 3-(4-hydroxyphenyl)lactate)] were associated with ≥1 dietary pattern. Candidate biomarkers of HEI, AHEI, and DASH distinguished individuals with highest compared with lowest quintile of diet scores beyond participant characteristics in samples 1 and 2 (P value for difference in C-statistics

A five-year-old male central bearded dragon (Pogona vitticeps) was presented for investigation of blood in the voided urates. A small cutaneous mass was detected in the gular region, but clinical examination was otherwise unremarkable. Fecal parasitology was negative. Initially, further diagnostics were declined, and antimicrobial treatment was initiated. At re-examination one month later, the gular mass had increased in size and an additional mass was detected within the celomic cavity. Both masses were surgically excised and diagnosed by histopathology as a high-grade anaplastic sarcoma (gular mass), resembling a histiocytic sarcoma, and a Sertoli cell tumor (coelomic mass). Neither of these have been previously reported in the central bearded dragon. Twenty months post-surgery, the lizard remains well with no recurrence of clinical signs or evidence of tumor re-growth.

Glenoid augmentation using free bone blocks for anterior shoulder instability has been proposed as an alternative to or bail-out for the Latarjet procedure. The purpose of this investigation was to systematically review and compare outcomes of patients undergoing glenoid augmentation using free bone block autografts versus allografts. A systematic review using PubMed, MEDLINE, Embase, and the Cochrane Library databases was performed in line with the PRISMA statement. Studies reporting outcomes of patients treated with free bone block procedures for anterior shoulder instability with minimum 2-year follow-up were included. Random effects modelling was used to compare patient-reported outcomes, return to sports, recurrent instability, non-instability related complications, and development of arthritis between free bone block autografts and allografts. Eighteen studies comprising of 623 patients met the inclusion criteria for this investigation. There were six studies reporting on the use of allografts (of these, two used distal tibial, three iliac crest, and one femoral head allograft) in 173 patients and twelve studies utilizing autografts (of these, ten used iliac crest and two used free coracoid autograft) in 450 patients. Mean age was 28.7 ± 4.1 years for the allograft group and 27.8 ± 3.8 years for the autograft group (n.s). Mean follow-up was 98 months in autograft studies and 50.8 months for allograft studies (range 24–444 months, n.s). Overall mean increase in Rowe score was 56.2 with comparable increases between autografts and allografts (n.s). Pooled recurrent instability rates were 3% (95% CI, 1–7%; I2 = 77%) and did not differ between the groups (n.s). Arthritic progression was evident in 11% of autografts (95% CI, 2–27%; I2 = 90%) and 1% (95% CI, 0–8%; I2 = 63%) of allografts (n.s). The overall incidence of non-instability related complications was 5% (95% CI, 2–10%; I2 = 81%) and was similar between the groups (n.s). Pooled return to sports rate was 88% (95% CI, 76–96%; I2 = 76%). Glenoid augmentation using free bone block autograft or allograft in the setting of recurrent anterior shoulder instability with glenoid bone loss is effective and safe. Outcomes and complication incidence using autografts and allografts were comparable. Due to the high degree of heterogeneity in the data and outcomes reported in available studies, which consist primarily of retrospective case series, future prospective trials investigating long-term outcomes using free bone block autograft versus allograft for anterior shoulder instability with glenoid bone loss are warranted. IV.

Autism spectrum disorder or autism is seen world-wide, however in Tanzania there is emerging awareness and understanding about the disorder among teachers. This study examines the knowledge outcomes of teachers after a multi-day training on autism at three sites across the country. A total of 99 teachers completed the training. At the end of the training, there was a significant increase in the knowledge scores on an autism knowledge measure across all sites. There was a significant difference in knowledge scores across sites, with teachers at one site scoring higher than teachers in both other sites. Reasons why are further discussed. This study provides a detailed description of how to increase the awareness of autism in the teaching community in Tanzania with positive outcomes.

Contains fulltext : 225322.pdf (Publisher’s version ) (Closed access) The generation of vascularized mineralized tissues of complex geometry without the use of extrinsic growth factors or exogenous cells requires a large animal model to recapitulate the challenges seen in the clinic. The proposed versatile ovine model can be utilized to investigate the use of a customized bioreactor to generate mineralized tissue, matching the size and shape of a defect before transfer to and integration within another site. The protocol results in bioreactors that can be harvested for investigation of the effects of different biomaterials for the generation of bone or to generate tissues appropriate for repair of bony defects; this protocol focuses on reconstruction of the mandible but could be modified for orthopedic applications. The bioreactor packing material can be altered, allowing for the study of various commercially available or novel graft materials. The surgical procedure requires ∼1.5 h to implant four bioreactors adjacent to rib periosteum. After 9 weeks, the harvest of the bioreactor tissue takes approximately 1 h. If creating a craniofacial defect, an additional 2 h should be taken for mandibular defect creation and 2 to 3 h for the reconstruction. Sheep that have undergone reconstruction are typically euthanized after 12 weeks to allow for evaluation of transferred tissues. In this protocol, we discuss the necessary steps to ensure the reproducibility and analytical techniques to assess bone regeneration such as microcomputed tomography, mechanical analysis, and histology. Impact statement Bone grafting is a frequent procedure in the fields of orthopedics, otolaryngology, and oral and maxillofacial surgery. Generating customized, vascularized, and mechanically robust bony tissues while eliminating common complications such as donor site morbidity with autograft harvest or lack of suitable mechanical properties with commercially available synthetic graft would greatly improve the lives of patients. A large animal model is necessary to generate tissues of clinically relevant geometries. In this article, a reproducible ovine model of in vivo bioreactor technology toward customized bone generation is presented with broad application to tissue engineering and regenerative medicine.

OBJECTIVE People living with HIV have an increased risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). Monocytes play a key role in the early stages of atherosclerosis-driven CVD by forming lipid-laden foam cells within artery walls. HIV infection potentiates foam cell formation ex vivo, but the mechanisms contributing to this are not known. METHODS We investigated the atherosclerosis-promoting potential of monocytes from 39 virologically suppressed men living with HIV (MLHIV) on ART and no evidence of CVD, and 25 HIV-uninfected controls of comparable age, sex, smoking status and CVD risk. RESULTS Despite absence of clinical atherosclerosis in both MLHIV and uninfected cohorts (evidenced by a carotid intima-media thickness of 0.6 mm for both groups; P = 0.254), monocytes from MLHIV showed increased potential to form atherosclerosis-promoting foam cells compared with controls in an ex-vivo assay (36.6% vs. 27.6%, respectively, P = 0.003). Consistent with observations of persistent inflammation and immune/endothelial activation in ART-treated HIV infection, levels of soluble tumour necrosis factor receptor II, CXCL10 and soluble VCAM-1 were elevated in MLHIV (P ≤ 0.005 for all), but were not significantly associated with foam cell formation. Foam cell formation was associated with an impaired ability of monocytes to undergo reverse transmigration, and a reduced ability to efflux cholesterol ex vivo (P

PURPOSE: As novel hormonal therapies, such as abiraterone and enzalutamide, move into earlier stages of treatment of advanced prostate cancer, there are significant cost implications. We used the ASCO Value Framework (AVF) and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) to quantify and compare the incremental clinical benefit and costs of these agents in the metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) settings. METHODS: We searched PubMed for randomized phase III trials of abiraterone and enzalutamide in mCRPC and mCSPC. Incremental clinical benefit was quantified using the AVF and ESMO-MCBS by 2 independent assessors. Incremental drug costs were calculated using average wholesale prices (AWPs) from the RED BOOK Online. RESULTS: In mCRPC, 2 abiraterone trials (COU-AA-301 and COU-AA-302) and 2 enzalutamide trials (AFFIRM and PREVAIL) met search criteria. AVF scores ranged from 46.3 to 66.6, suggesting clinical benefit; ESMO-MCBS scores ranged from 3 to 5, with lower clinical benefit in the mCRPC predocetaxel setting. The overall incremental AWP ranged from $83,460.94 to $205,128.85. In mCSPC, 4 trials met criteria (LATITUDE, STAMPEDE, ENZAMET, and ARCHES; AVF scores were 79.8, 33.3, 59, and 17, respectively). All of the studies showed benefit except ARCHES. By ESMO-MCBS, both LATITUDE and STAMPEDE showed benefit (score for 4 for both studies); ENZAMET and ARCHES were not evaluable. The overall cost of treatment was significantly higher in the mCSPC setting. CONCLUSION: The AVF and ESMO-MCBS frameworks generated slightly different results but suggested that abiraterone and enzalutamide show clinical benefit in both mCRPC and mCSPC but trended to lower clinical benefit and increased costs in earlier disease stages. Further refinement of the AVF and ESMO-MCBS is needed to facilitate their use and their ability to inform clinical practice in a rapidly changing treatment landscape.

Background:Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes.Objective:Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications.Methods:The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment.Results:The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload.Conclusions:The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

Focal articular cartilage defects are a significant source of pain and dysfunction in the knee, affecting upwards of one million people and resulting in an increased incidence of cartilage surgeries performed each year. To address these defects, several operative techniques are commonly utilized depending on defect site and location. While specific treatment choice and technique are individualized, cartilage procedures can broadly be classified as palliative measures such as chondroplasty, repair procedures such as microfracture, and restorative procedures including autologous chondrocyte implantation (ACI), osteochondral autograft transplantation (OATS), and osteochondral allograft transplantation.

Anterior cruciate ligament (ACL) injuries are a common knee pathology with a high associated cost. The incidence of ACL injury is sex-, age-, and sport-dependent. For this common injury, it is necessary to understand associated costs for different treatments. ACL reconstruction is the definitive, surgical treatment option for an ACL injury; however, given the ubiquity of ACL reconstructions, it is important to understand the most cost-effective technique for each patient. This chapter will explore the frequency and incidence of primary and recurrent ACL injury in specific patient populations. In addition, it will review the current literature on the costs associated with treating ACL injuries from both a nonoperative and surgical standpoint, and how to minimize costs through injury prevention.

Purpose of ReviewMassive irreparable rotator cuff tears present a significant challenge to the orthopedic surgeon. No single treatment, particularly among joint-preserving options, has been shown to be superior. The purpose of this review is to discuss recent advances in the treatment of massive irreparable rotator cuff tears, including partial repair with and without graft augmentation, interposition grafts, superior capsule reconstruction, subacromial balloon spacers, tendon transfer, and reverse total shoulder arthroplasty. We will also offer guidance on surgical indications based on our clinical experience.Recent FindingsPartial repair may offer reasonable clinical improvement for patients with lower preoperative function despite high re-tear rates. Additionally, several types of interposition grafts have shown promising short-term results and may outperform repair alone. Subacromial balloon spacers may lead to clinical improvement, especially in patients without glenohumeral osteoarthritis or pseudoparalysis, and recently received FDA approval for use in the USA. Superior capsule reconstruction is a technically demanding procedure that appears to produce excellent short-term results particularly when performed at high volume, but long-term studies in heterogeneous study groups are needed. Tendon transfers improve function by restoring force coupling in the shoulder, offering a promising option for younger patients. Reverse total shoulder arthroplasty (RTSA) is a reliable option for treatment of irreparable cuff tears in elderly patients with lower functional demands.SummaryIrreparable cuff tears remain a difficult condition to treat. Recommended treatment for younger patients without glenohumeral osteoarthritis is particularly controversial. For older patients with low-demand lifestyles and glenohumeral osteoarthritis, RTSA is an effective treatment option. For all discussed procedures, patient selection appears to play a critical role in clinical outcomes.

Neuroblastoma is the commonest extracranial pediatric malignancy. With few recurrent single nucleotide variations (SNVs), mutation-based precision oncology approaches have limited utility, but its frequent and heterogenous copy number variations (CNVs) could represent genomic dependencies that may be exploited for personalized therapy. Patient-derived cell culture (PDC) models can facilitate rapid testing of multiple agents to determine such individualized drug-responses. Thus, to study the relationship between individual genomic aberrations and therapeutic susceptibilities, we integrated comprehensive genomic profiling of neuroblastoma tumors with drug screening of corresponding PDCs against 418 targeted inhibitors. We quantified the strength of association between copy number and cytotoxicity, and validated significantly correlated gene-drug pairs in public data and using machine learning models. Somatic mutations were infrequent (3.1 per case), but copy number losses in 1p (31%) and 11q (38%), and gains in 17q (69%) were prevalent. Critically, in-vitro cytotoxicity significantly correlated only with CNVs, but not SNVs. Among 1278 significantly correlated gene-drug pairs, copy number of GNA13 and DNA damage response genes CBL, DNMT3A, and PPM1D were most significantly correlated with cytotoxicity; the drugs most commonly associated with these genes were PI3K/mTOR inhibitor PIK-75, and CDK inhibitors P276-00, SNS-032, AT7519, flavopiridol and dinaciclib. Predictive Markov random field models constructed from CNVs alone recapitulated the true z-score-weighted associations, with the strongest gene-drug functional interactions in subnetworks involving PI3K and JAK-STAT pathways. Together, our data defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. Integration of genomic profiling and drug screening of patient-derived models of neuroblastoma can quantitatively define copy number-dependent sensitivities to targeted inhibitors, which can guide personalized therapy for such mutationally quiet cancers.

INTRODUCTION AND OBJECTIVE:Metabolic syndrome (MetS) has been shown to increase prostate cancer (PC) risk, but association between MetS and PC outcomes after radical prostatectomy (RP) is poorly es...

Osteonecrosis of the femoral head (ONFH) is a disease in which inadequate blood supply to the subchondral bone causes the death of cells in the bone marrow. Decalcified histology and assessment of the percentage of empty lacunae are used to quantify the severity of ONFH. However, the current clinical practice of manually counting cells is a tedious and inefficient process. We utilized the power of artificial intelligence by training an established deep convolutional neural network framework, Faster-RCNN, to automatically classify and quantify osteocytes (healthy and pyknotic) and empty lacunae in 135 histology images. The adjusted correlation coefficient between the trained cell classifier and the ground truth was R = 0.98. The methods detailed in this study significantly reduced the manual effort of cell counting in ONFH histological samples and can be translated to other fields of image quantification.

Background and aims When patients with sickle cell disease have appropriate indications, they can be prescribed hydroxyurea (HU) and deferasirox (DFX) concurrently despite little knowledge about how the two medications interact. We wished to analyze whether there was evidence of adverse interaction between HU and DFX when taken simultaneously and hypothesized that those who took both drugs together had similar clinical complications when compared to those who took only one or neither drug. Methods We conducted this retrospective cohort investigation between 2009 and 2016 of persons with SCD in the California Sickle Cell Data Collection Program, a validated database of Californians with SCD a statewide. People in the database who took HU and DFX simultaneously for at least 3 months as compared to those who took either HU or DFX alone or to matched persons who took neither drug were eligible. Results We identified 104 people who were prescribed both HU and DFX concurrently, 877 who were prescribed HU only, and 314 who were prescribed DFX only during the study period. We identified 416 matched controls who took neither HU nor DFX. People who took both HU and DFX concurrently had similar rates of ED and inpatient encounters and had similar rates and distribution of adverse effects compared to those who took either HU or DFX alone or took neither drug. Conclusion Three months of concurrent use of DFX and HU appears safe, but further studies are required to better understand the safety and effectiveness of this medication combination. (Funded by CDC, CDC Foundation, and others).

The Latarjet procedure to treat instability was first described by the eponymous surgeon in 1954. Long-term results from this procedure have been favorable. In 2007, Lafosse et al. first described an all-arthroscopic technique for the Latarjet procedure. In the United States, the Latarjet procedure is most predictably indicated by surgeons in cases of significant glenoid bone loss, revision instability, and patients engaging in high-risk sport. In some European centers, the Latarjet has broader indications and is often also used as a first-line surgical intervention when conservative treatment has failed, including for those without bone loss or with multidirectional instability. • Achieve exposure of the inferior pole of coracoid and anterior glenoid rim; • coracoid is prepared; axillary nerve and brachial plexus are exposed; • coracoid portal is created; • coracoid is drilled and osteotomy is made; • coracoid transferred to anterior glenoid rim through split in subscapularis; • the bone graft is fixed in place with screws. Arthroscopic Latarjet can have a difficult learning curve compared with the open procedure. Both arthroscopic and open Latarjet have similar complication rates. The most common complications include graft fracture, non-union, and infection and are less than 2%. Arthroscopic Latarjet is reported to be less painful initially, but this equalizes by 1 month. Studies have shown that arthroscopic Latarjet results in excellent graft position. Recurrent instability for arthroscopic Latarjet ranges from 0.3% to 4.8% and is comparable with open Latarjet procedures. In summary, the arthroscopic Latarjet procedure results in less pain early, excellent coracoid graft position, and has a similar complication rate to open Latarjet.

Digital imaging technology and refined software programs have significantly improved a clinician's ability to assess and evaluate anatomic structures and quantify both defect size and required graft volume. This article summarizes the computed tomography-based technology used in these applications to illustrate their current use as exemplified by computer-assisted planning and treatment of severe maxillofacial atrophy treated using both interpositional and mesh-onlay grafting methodology.

Cognitive performance and cerebral hemispheric function are known to vary with fluctuating levels of estradiol and progesterone across the menstrual cycle in naturally cycling females. However, the literature is mixed with regard to how each hemisphere may be affected by elevated ovarian hormones. To better understand this, the current study employed a dual-task paradigm to examine potential shifts in hemispheric involvement for a verbal problem-solving task across the menstrual cycle in 30 right-handed, normally cycling young adult females (18–21 years old). To our knowledge, no study to date has utilized dual-task procedures to directly investigate the potential shifts in hemispheric function across the menstrual cycle. Specifically, participants were tested during both menses and their estimated midluteal phase where they engaged in repetitive unilateral finger-tapping while concurrently solving anagrams silently or aloud. Analysis of finger-tapping interference during the dual-task conditions revealed that solving anagrams silently was lateralized to the left hemisphere while solving anagrams aloud yielded a pattern of more bilateral hemispheric involvement, both of which were consistent across both menses and midluteal phases. Analysis of cognitive performance, however, revealed that silent anagrams performance while tapping with the right, but not left, hand significantly increased during the midluteal phase. Consistent with a number of other studies using different methodological approaches, the current dual-task findings suggest that when ovarian hormone levels are putatively elevated, there is enhanced recruitment of left hemisphere resources while performing a lateralized verbal task.

Summary Introduction Extracellular vesicles (EVs) are cell-secreted packages that deliver cargo to target cells to effect functional and phenotypic changes. They are secreted by many different cell types, including adipose-derived stem cells (ADSCs), which are a promising field of study in regenerative medicine. Our aim was to perform a systematic review of the literature to summarize the scientific work that has been conducted on ADSC EVs to date. Methods The Pubmed database was queried with keywords (and variations of) “adipose derived stem cell,” “stromal vascular fraction,” and “extracellular vesicles.” We excluded review papers, then manually screened articles based on title and abstract. Full-text articles were assessed for eligibility to include in final review. Results While an extensive body of research exists on EVs, a much smaller proportion of that is original research on ADSC EVs. Of 44 manuscripts that met our database search criteria, 21 articles were selected for our systematic review. Conclusion ADSC EVs were found to exert effects on angiogenesis, cell survival and apoptosis, inflammation, tissue regeneration, and reduction of disease pathology. Further studies examine characteristics of ADSC EVs. Future work should aim to further detail the safety profiles of ADSC EVs given their potential for cell-based therapies. The body of research studies characterizing ADSC EVs continues to expand, and much work remains to be done before human pilot studies can be considered. To our knowledge, we offer the first systematic review summarizing the research on ADSC EVs and their determined roles to date.

Bariatric surgery (BS) produces superior weight loss compared to non-surgical interventions. However, studies suggest bariatric patients who have undergone gastric-bypass surgery have an increased risk of developing new onset substance use disorder (SUD) or suffer negative outcomes after surgery. As such, many bariatric programs consider alcohol/ illicit drug misuse a contraindication to BS. The purpose of this systematic review was to investigate weight loss outcomes, post-surgery substance use patterns and other morbidity/mortality in BS patients with a history of substance use/SUD. Studies were identified by searching Ovid Medline(R), Embase, and PsychInfo. We included all study types investigating humans of any age/sex who had undergone any BS procedure with data regarding substance use before and/or after surgery. Outcome measures included metabolic outcomes and psychiatric outcomes after bariatric surgery in patients reporting substance use prior to bariatric surgery and substance use patterns after bariatric surgery. Fifty-eight studies were included in the review. Studies reporting weight loss after BS did not demonstrate an association between substance use and negative weight loss outcomes. Several studies reported a significant portion of participants having new onset or increased substance use after BS. Factors associated with new onset or increased substance use/SUD after BS included the type of surgery, a history of SUD, a family history of SUD, coping skills/life stressors, age, male sex and alcohol sensitization after surgery. Substance use history does not appear to influence weight loss after BS, however it may contribute to increased substance use after BS. Clinicians should ensure valid screening tools when assessing BS candidates for substance use history and ensure long term follow-up care post-operatively.

International audience; Brain data recorded with electroencephalography (EEG), magnetoencephalography (MEG) and related techniques often have poor signal-to-noise ratios due to the presence of multiple competing sources and artifacts. A common remedy is to average responses over repeats of the same stimulus, but this is not applicable for temporally extended stimuli that are presented only once (speech, music, movies, natural sound). An alternative is to average responses over multiple subjects that were presented with identical stimuli, but differences in geometry of brain sources and sensors reduce the effectiveness of this solution. Multiway canonical correlation analysis (MCCA) brings a solution to this problem by allowing data from multiple subjects to be fused in such a way as to extract components common to all. This paper reviews the method, offers application examples that illustrate its effectiveness, and outlines the caveats and risks entailed by the method.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Engineered magnetic nanoparticles (MNPs) are emerging as advanced tools for medical applications. The coating of MNPs using polyelectrolytes (PEs) is a versatile means to tailor MNP properties and is used to optimize MNP functionality. Dendritic cells (DCs) are critical regulators of adaptive immune responses. Functional distinct DC subsets exist either under steady-state or inflammatory conditions, which are explored for the specific treatment of various diseases, such as cancer, autoimmunity or transplant rejection. Here, the impact of PE coating of ferumoxytol for uptake into both inflammatory and steady-state DCs and cellular responses to the MNP labeling is addressed. Labeling efficiency by uncoated and PE-coated ferumoxytol is highly variable in different DC subsets, and PE coating significantly improves the labeling of steady-state DCs. Uncoated ferumoxytol results in increased cytotoxicity of steady-state DCs after labeling that is abolished by the PE coating, while no increased cell death is observed in inflammatory DCs. Furthermore, uncoated and PE-coated ferumoxytol appears immunologically inert in inflammatory DCs but induces activation of steady-state DCs. These results show that PE coating of MNPs can be applied to endow particles with desired properties for enhanced uptake and cell type-specific responses in distinct target DC populations.

Background: Medial patellofemoral ligament (MPFL) reconstruction is a common surgical treatment for patients with recurrent patellar instability. A variety of risk factors, such as age, trochlear dysplasia, patella alta, and increased tibial tubercle–trochlear groove (TT-TG) distance, have been identified and may lead to postoperative failure or poor outcomes. Purpose: While a large number of risk factors have been identified, significant heterogeneity exists in evaluating and reporting these risk factors in the literature. The goal of this study was to perform a systematic review to determine risk factors associated with worse outcomes after MPFL reconstruction and their consistency of being controlled for or analyzed among studies. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the literature was performed using the MEDLINE database to identify relevant clinical outcome studies after MPFL reconstruction for recurrent patellar instability. Eligible studies were evaluated for risk factors that were associated with MPFL failure, defined as recurrent instability or lack of improvement on patient-reported outcome (PRO) scores. Each study was then evaluated for inclusion of these risk factors. Results: Ten studies were included in the final analysis, comprising 1287 knees from 1275 patients who underwent isolated MPFL reconstruction. Of these 10 studies, 8 defined outcomes based on PROs and 3 defined outcomes based on postoperative recurrent instability (1 study included both outcomes). In the PRO failure group, 12 risk factors were found across all studies: trochlear dysplasia, trochlear bump height, elevated TT-TG, patellar tilt, hyperlaxity, age at first dislocation, age at surgery, body mass index, bilateral symptoms, WARPS/STAID score (weak atraumatic, risky anatomy, pain, and subluxation/strong, traumatic, anatomy normal, instability, and dislocation), femoral tunnel malposition, and femoral tunnel widening. In the recurrent instability failure group, 7 risk factors were found across all studies: trochlear dysplasia, bump height, patella alta, higher sulcus angle, higher congruence angle, preoperative J sign, and femoral tunnel malposition. Trochlear dysplasia and femoral tunnel malposition were consistently cited in several studies as risk factors for worse PROs and higher rates of recurrent instability. Patella alta was indicated as a significant risk factor for recurrent instability in 1 of 2 studies analyzing postoperative instability failures and was not associated with worse PROs in any of the studies analyzed. Similarly, elevated TT-TG distance was not a significant risk factor in any of the studies that analyzed recurrent instability as the failure endpoint. Conclusion: While various risk factors are postulated to affect outcomes after MPFL reconstruction, there remains inconsistency within the literature regarding the inclusion of all risk factors in a given analysis. Furthermore, the significance of these risk factors varies among studies in terms of whether they affect postoperative outcomes. We found that more severe trochlear dysplasia (types C and D) and femoral tunnel malposition (>10 mm from Schöttle’s point) appear to have the most consistent effect on producing higher rates of recurrent dislocation as well as worse PROs. Despite this, the role of concomitant bony procedures to adjust certain pathoanatomic risk factors in addition to MPFL reconstruction remains unknown. Future high-level studies must be conducted that respect the multifactorial nature of patellar instability and should analyze all risk factors (demographic, anatomic, and radiographic) reported to affect outcomes.

Purpose The purpose of this study was to compare outcomes after hip arthroscopy for FAIS in patients with borderline hip dysplasia and hip instability defined radiographically using the femoroepiphyseal acetabular roof (FEAR) index, and patients without radiographic evidence of hip instability. Methods Data from consecutive patients with borderline hip dysplasia (lateral center edge angle, LCEA, 18˚-25˚) who underwent primary hip arthroscopy between April 2012 and June 2017 for the treatment of femoroacetabular impingement syndrome (FAIS) were analyzed. Baseline demographic data, radiographic parameters, preoperative, and two-year postoperative patient reported outcome measures (PROM) were collected. FEAR index was measured by three different observers. Patients with an average FEAR index ≥2˚ were categorized as having radiographic evidence of instability as previously published. The analysis was powered to detect a minimal clinical important difference (MCID) for each outcome score. Statistical analysis was performed as appropriate to compare patients with FEAR index ≥2 and Results A total of 140 patients met the inclusion criteria. The average age and body mass index of included patients was 31.7±13.2 (p 0.05 for all). Conclusion Patients with borderline hip dysplasia and radiographic-evidence of hip instability, as measured by the FEAR index (≥2°), achieve similar improvement in 2-year outcomes compared to those with radiographically stable hips following arthroscopic treatment of FAIS.

Background The physical decrements of aging predispose older adults to falls and fall-related injuries. Consequences of falling place financial and logistical burdens on the health care system. With an aging population, mitigation of risk and reduction of harm are important objectives. Studies show that exercise can improve balance and build muscle mass. The challenge is prescribing safe and evidence-based exercise regimens to older adults. Objectives The objective of this evidence review was to determine if an exercise program can reduce fall rates and prolong functional independence among older adults living in the community. Data sources This review included 14 randomized control trials and one quasi-experimental interventional study, all published between 2014 and 2020. Conclusions The evidence suggests that a home- or community-based exercise program with formal instruction and health care provider involvement can be an effective fall-prevention and harm reduction strategy for community-dwelling older adults. Implications for practice The evidence suggests that a home- or community-based exercise program may be an effective fall-prevention strategy for older adults living independently in the community. Health care providers should educate these patients about the benefits of exercise as a fall-prevention measure and assist patients in increasing participation in exercise programs by making referrals and promoting engagement in evidence-based exercise programs.

Antibiotic-releasing porous poly(methyl methacrylate) (PMMA) space maintainers, comprising PMMA with an aqueous porogen and a poly(DL-lactic-co-glycolic acid) (PLGA) antibiotic carrier, have been developed to facilitate local delivery of antibiotics and tissue integration. In this study, clindamycin-loaded space maintainers were used to investigate the effects of antibiotic release kinetics and dose upon bacterial clearance and bone and soft tissue healing in a pathogen-contaminated rabbit mandibular defect. Three formulations were fabricated for either high dose burst release (7 days) or with PLGA microparticles for extended release (28 days) at high and low dose. Although inoculated bacteria were not recovered from any specimens, the burst release formulation showed less inflammation and fibrous capsule formation and more bone formation close to the implant than the low dose extended release formulation by histologic analysis. These results suggest that local antibiotic release kinetics and dose affect ...

To report contemporary trends in hip arthroscopy case volume in the United States using a large cross-sectional cohort with accurate laterality tracking for assessment of revision surgery and rates of conversion to total hip arthroplasty (THA).Using Current Procedural Terminology codes, we queried the Mariner PearlDiver dataset for patients who underwent hip arthroscopy from 2010 to 2017. Patient demographics were recorded and subsequent hip arthroscopy procedures and THA conversion within 2 years after surgery were tracked using International Classification of Diseases, Tenth Revision codes to accurately identify laterality. Emergency department and hospital admission within 30 days after surgery were queried.Of the 53,103 patients undergoing hip arthroscopy procedures, hip arthroscopy case volume increased 2-fold from 2010 to 2014 but remained relatively unchanged from 2014 to 2017. The most common age group undergoing surgery was 40 to 49 years, and female patients represented 70% of cases. Two-year subsequent surgery rate was 19%, with 15.1% undergoing a revision arthroscopy and 3.9% converting to THA. The most common revision arthroscopy procedures were femoroplasty (9.5%), labral repair (8.5%), and acetabuloplasty (4.3%). Younger patients were more likely to undergo revision arthroscopy (18% age 10-19 years; 15% age 20-29 years). Older patients had a significant risk for conversion to THA within 2 years (36% age 60-69 years; 28% age 50-59 years). Female patients also demonstrated a slightly greater rate of conversion to THA (4.1% female, 3.5% male, P.0001). Patients 20 to 29 years had the greatest risk of emergency department admission (5.4%) and hospital admission (0.8%) within 30 days of surgery.The rise in hip arthroscopy procedures may be starting to plateau in the United States. Cross-sectional data also indicate that there is a greater than previously reported rate of revision hip arthroscopy in patients younger than 30 years of age and conversion to THA in patients older than 50 years of age.III, cross-sectional study.

Perceptual processes can be probed by fitting stimulus-response models that relate measured brain signals such as electroencephalography (EEG) to the stimuli that evoke them. These models have also found application for the control of devices such as hearing aids. The quality of the fit, as measured by correlation, classification, or information rate metrics, indicates the value of the model and the usefulness of the device. Models based on Canonical Correlation Analysis (CCA) achieve a quality of fit that surpasses that of commonly-used linear forward and backward models. Here, we show that their performance can be further improved using several techniques, including adaptive beamforming, CCA weight optimization, and recurrent neural networks that capture the time-varying and context-dependent relationships within the data. We demonstrate these results using a match-vs-mismatch classification paradigm, in which the classifier must decide which of two stimulus samples produced a given EEG response and which is a randomly chosen stimulus sample. This task captures the essential features of the more complex auditory attention decoding (AAD) task explored in many other studies. The new techniques yield a significant decrease in classification errors and an increase in information transfer rate, suggesting that these models better fit the perceptual processes reflected by the data. This is useful for improving brain-computer interface (BCI) applications.

Historically, microfracture was a commonly utilized procedure for treating small focal chondral defects of the knee. However, studies have demonstrated that microfracture lacks long-term durability. Despite this, microfracture remains the most commonly performed cartilage repair treatment due to its technical ease, cost-effectiveness, and the ability to be performed as a one-stage procedure. Over the last decade, novel techniques for augmenting microfracture to improve long-term outcomes have emerged. These approaches fall into two main categories: scaffolds and orthobiologics. The goal of both of these augmentations is to improve cartilage fill and durability, thereby improving long-term outcomes. Scaffolds provide a structure for cell proliferation and can be applied with a sealant to inhibit extravasation of bone marrow elements into the joint after marrow stimulation. The goal of orthobiologics is to increase the availability of cytokines and cells necessary for cartilage development. This chapter will explore the current landscape of microfracture augmentation with a focus on scaffold and orthobiologic augmentation.

Osteochondral defects present a unique clinical challenge due to their combination of phenotypically distinct cartilage and bone, which require specific, stratified biochemical cues for tissue regeneration. Furthermore, the articular cartilage exhibits significantly worse regeneration than bone due to its largely acellular and avascular nature, prompting significant demand for regenerative therapies. To address these clinical challenges, we have developed a bilayered, modular hydrogel system that enables the click functionalization of cartilage- and bone-specific biochemical cues to each layer. In this system, the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT) was click conjugated with either a cartilage- or bone-specific peptide sequence of interest, and then mixed with a suspension of thermoresponsive polymer and mesenchymal stem cells (MSCs) to generate tissue-specific, cell-encapsulated hydrogel layers targeting the cartilage or bone. We implanted bilayered hydrogels in rabbit femoral condyle defects and investigated the effects of tissue-specific peptide presentation and cell encapsulation on osteochondral tissue repair. After 12 weeks implantation, hydrogels with a chondrogenic peptide sequence produced higher histological measures of overall defect filling, cartilage surface regularity, glycosaminoglycan (GAG)/cell content of neocartilage and adjacent cartilage, and bone filling and bonding compared to non-chondrogenic hydrogels. Furthermore, MSC encapsulation promoted greater histological measures of overall defect filling, cartilage thickness, GAG/cell content of neocartilage, and bone filling. Our results establish the utility of this click functionalized hydrogel system for in vivo repair of the osteochondral unit.

Supplemental Digital Content is available in the text., Introduction: Sickle cell disease is a complex chronic disorder associated with increased morbidity and early mortality. The Pediatric Quality Measures Program has developed new sickle cell-specific quality measures focused on hydroxyurea (HU) counseling and annual transcranial Doppler (TCD) screening; however, these measures have not been used in a clinical setting to inform quality improvement (QI) efforts. Methods: From 2017 to 2018, 9 sickle cell subspecialty clinics from the Pacific Sickle Cell Regional Collaborative conducted a year-long QI collaborative focused on improving the percentage of patients with HU counseling and TCD screening based on the new quality measures. After an initial kick-off meeting, the 9 sites participated in monthly conference calls. We used run charts annotated with plan-do-study-act cycle activities to track each site’s monthly progress and the overall mean percentage for the entire collaborative. Results: There was an overall improvement in the aggregate HU counseling from 85% to 98% (P < 0.01). For TCD screening, referral frequency changed from 85% to 90% (P = 0.76). For both measures, the variation in frequencies decreased over the year. Conclusion: Over 1 year, we found that a regional QI collaborative increased HU counseling. Although referral for TCD screening increased, there was no overall change in TCD completion. Overall, this QI report’s findings can help clinicians adopt and implement these quality measures to improve outcomes in children.