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OBJECTIVE Endovascular aortic repair (EVAR) can treat anatomically compatible ruptured abdominal aortic aneurysms (rAAA), but registry data suggests that women undergo more open abdominal aneurysm repairs than men. We evaluate in-hospital outcomes of EVAR for rAAA by sex. METHODS The Vascular Quality Initiative (VQI) registry was queried from 2013 to 2019 for rAAA patients treated with EVAR. Univariate analysis was performed with Student's t-test and chi-squared tests. Multivariable logistic regression was then performed to assess the association between female sex and inpatient mortality. RESULTS 1775 patients were included (23.8% female). Female rAAA patients were older (p < 0.01) and weighed less (p < 0.01). They were less likely to have smoked (p

Purpose: International data demonstrate association between clinical trial participation and reduced cancer mortality. Adolescents and young adults (AYA) have low clinical trial enrollment rates. We established a program to understand local barriers and develop targeted solutions that lead to greater AYA clinical trial participation. Methods: A steering committee (SC) with expertise in adult and pediatric oncology, research ethics, and consumer representation was formed. The SC mapped barriers related to AYA trial access and established working groups (WGs) around three themes. Results: The Regulatory Awareness WG identified a lack of understanding of processes that support protocol approval for clinical trials across the AYA age range. A guideline to raise awareness was developed. The Access WG identified challenges for young adults (18-25 years) to access a pediatric hospital to enroll in a pediatric trial. A procedure was developed to streamline applications for access. The first six applications using this procedure have been successful. The Availability WG identified lack of pediatric-adult oncology reciprocal relationships as a barrier to awareness of open trials, and future collaboration. An AYA Craft Group Framework was established to grow relationships within tumor streams across institutions; two craft groups are now operating locally. An additional achievement was a successful request to the Therapeutic Goods Administration for Australian adoption of the Food and Drug Administration Guidance on Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. Conclusion: This multipronged approach to improving AYA clinical trial access has relevance for other health environments. Our knowledge products are available as an online toolkit.

OBJECTIVES Patients with abdominal aortic aneurysms undergoing EVAR with larger device diameters (34- to 36-mm) have worse outcomes due to proximal fixation failure and need for reintervention. We examine outcomes relating to standard fenestrated repair (FEVAR) with larger device diameters, and investigate whether a similar relationship exists. MATERIAL AND METHODS Retrospective review of a prospectively maintained, single institution database of patients treated with the Cook ZFEN device between 2012-2017. Outcomes were stratified by device diameter into normal-diameter (ND,≤ 32 mm) and large-diameter (LD,34-36 mm). Primary endpoints were need for reintervention and composite type I/III endoleak. RESULTS 100 consecutive patients treated were identified for inclusion. Overall mean age was 73.6 years and mean aortic diameter was 59.1 mm. Mean follow-up was 22 months. A total of 26 (26%) patients were treated with LD devices. Number of target vessels per patient was 2.8 in both groups. Infrarenal neck length and diameter were significantly different in the LD and ND patients, respectively (2.6 mm vs 4.7 mm (P

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p

Purpose The effects of neuromodulation are virtually unexplored in adductor laryngeal dystonia (AdLD), a disorder characterized by involuntary contraction of intrinsic laryngeal muscles. Recent findings indicated that intracortical inhibition is reduced in people with AdLD. Low-frequency repetitive transcranial magnetic stimulation (rTMS) induces prolonged intracortical inhibition, but the effects in AdLD are unexplored. This pilot and feasibility study aimed to examine the safety, feasibility, and effects of a single session 1 Hz rTMS over the laryngeal motor cortex (LMC) in people with AdLD and healthy individuals. Methods The stimulation location was individualized and determined through TMS-evoked responses in the thyroarytenoid muscles using fine-wire electrodes. 1200 pulses of 1 Hz rTMS were delivered to the left LMC in two groups: Control (n = 6) and AdLD (n = 7). Tolerance, adverse effects, intracortical inhibition, and voice recordings were collected immediately before and after rTMS. Voice quality was assessed with acoustic-based and auditory-perceptual measures. Results All participants tolerated the procedures, with no unexpected adverse events or worsening of symptoms. No significant effects on intracortical inhibition were observed. In the AdLD group, there was a large-effect size after rTMS in vocal perturbation measures and a small-effect size in decreased phonatory breaks. Conclusions One rTMS session over the LMC is safe and feasible, and demonstrated trends of beneficial effects on voice quality and phonatory function in AdLD. These preliminary findings support further investigation to assess clinical benefits in a future randomized sham-controlled trial. ClinicalTrials.gov NCT02957942, registered on November 8, 2016.

Purpose To analyze recent trends in orthopaedic surgery consolidation and quantify these changes temporally and geographically from 2012 to 2020. Methods We performed a retrospective cross-sectional analysis of orthopaedic surgeon practice size in the United States using 2012 and 2020 data obtained from the Physician Compare database. Results Although we observed an increase from 21,216 unique orthopaedic surgeons in 2012 to 21,553 in 2020 (1.6% increase), the number of practices experienced a large decrease from 7,299 practices in 2012 to 5,829 in 2020 (20.1% decrease). The proportion of orthopaedic surgeons working in solo practices decreased from 13.2% (2,790) in 2012 to 7.4% (1,595) in 2020, and the proportion of orthopaedic surgeons working in groups sized 2 to 24 decreased from 35.3% (7,482) in 2012 to 22.2% (4,775) in 2020. In contrast, groups sized 25 to 99 have grown from 20.7% (4,387) of all orthopaedic surgeons to 23.4% (5,048) in 2020. Groups sized 100 to 499 have increased from 16.9% (3,593) in 2012 to 24.1% (5,190) in 2020, whereas groups sized 500 or greater have grown from 14% (2,964) in 2012 to 22.9% (4,945) in 2020. The number of unique group practices showed a significant decrease in the number of solo groups, which comprised 43.8% (3,200) of the total number of individual practices in 2012, decreasing to 32% (1,886) in 2020. All other groups increased in number and proportionally from 2012 to 2020. Conclusions This study shows that over the period from 2012 to 2020, there has been a substantial trend of orthopaedic surgeons shifting to increasing practice sizes, potentially indicating that more orthopaedic surgeons are working for large health care organizations rather than small independent practices. Clinical Relevance The impact of these changes should be examined to determine large-scale effects on patient care, payment models, access, and outcomes, along with physician compensation, lifestyle, and satisfaction.

Background Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. Methods Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). Results As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3–79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16–49) for all patients. The 24-week disease control rate was 73% (95% CI: 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45–100), 56% (95% CI: 38–74), and 85% (95% CI: 71–99), respectively. Median time to response was 1.9 months (range 1.0–3.8 months). Duration of treatment ranged from 1.2–31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3–4 in 3 patients. No new safety signals were identified. Conclusions In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.

Background Obesity is a widely accepted risk factor for the development of severe COVID-19. We sought to determine the survival benefit of early initiation of aggressive anticoagulation in obese critically ill COVID-19 patients. Methods We retrospectively reviewed 237 intubated patients at a single academic accredited bariatric center and stratified them based on their BMI into 2 groups, obese (BMI > 30) and non-obese (BMI ≤ 30). We used chi-square tests to compare categorical variables such as age and sex, and two-sample t-tests or Mann Whitney U-tests for continuous variables, including important laboratory values. Cox proportional-hazards regression models were utilized to determine whether obesity was an independent predictor of survival and multivariable analysis was performed to compare risk factors that were deemed significant in the univariable analysis. Survival with respect to BMI and its association with level of anticoagulation in the obese cohort was evaluated using Kaplan–Meier models. Results The overall mortality in the obese and non-obese groups was similar at 47% and 44%, respectively (p = 0.65). Further analysis based on the level of AC showed that obese patients placed on early aggressive AC protocol had improved survival compared to obese patients who did not receive protocol based aggressive AC (ON-aggressive AC protocol 26% versus OFF-aggressive AC protocol 61%, p = 0.0004). Conclusions The implementation of early aggressive anticoagulation may balance the negative effects of obesity on the overall mortality in critically ill COVID-19 patients. Graphical abstract

PURPOSE Precision medicine uses advanced molecular techniques to guide the use of targeted therapeutic drugs and is an emerging paradigm in pediatric oncology. Clinical evidence related to the efficacy of many novel targeted drugs, however, is currently very limited given the rarity of pediatric cancer and the lack of published evidence for the use of these drugs in children. This systematic review aimed to evaluate the existing evidence for the feasibility and clinical efficacy of precision medicine in pediatric oncology. METHODS A systematic review was conducted using the PubMed, Medline, and Embase databases. Clinical trials and observational studies, which used molecular assays such as whole-exome sequencing to identify molecular targets that guided the allocation of targeted cancer drugs and reported clinical outcomes, were included in this review. RESULTS Twenty-one clinical trials and observational studies were identified, collectively enrolling 1,408 pediatric patients across nine countries. Therapeutic targets were found in 647 patients (46.0%); however, only 175 of these patients (27.0%) received a targeted drug. Objective responses were recorded for 73 (41.7%) of these 175 patients, only 5.2% of the total sample. Inconsistent outcome reporting and limited comparison with conventional treatment hindered evaluation of the clinical utility of precision medicine. CONCLUSION Precision medicine can feasibly identify molecular targets in a clinical setting. However, the inaccessibility of targeted drugs is a significant barrier, restricting the exploration of its therapeutic potential in pediatric oncology. Future clinical trials should endeavor to link the molecular testing results with access to targeted drugs and standardize outcome reporting to advance understanding of the benefits of this novel paradigm in improving patient outcomes.

Background Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. Methods Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, Results Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. Conclusions The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

Lefamulin is a novel antibiotic agent within the pleuromutilin derivative class approved for the treatment of community-acquired bacterial pneumonia (CABP) by the United States Food and Drug Administration (FDA) and the European Commission (EC) in 2019 and 2020, respectively. The objective of this article is to provide a summary of clinically relevant data underlying lefamulin, and to provide recommendations for its place in therapy. In vitro data establishes lefamulin's activity against a number of gram-positive, gram-negative, and atypical organisms relevant in the treatment of CABP, including S. pneumoniae, H. influenzae, M. catarrhalis, L. pneumophila, M. pneumoniae, and C. pneumoniae. Two phase 3 studies, the Lefamulin Evaluation Against Pneumonia (LEAP) trials, established non-inferiority of lefamulin against moxifloxacin in the treatment of CABP, including sequential transition from intravenous to oral therapy and across a broad set of patient demographics and severities. Pooled and post-hoc analyses have confirmed these effects for a variety of subgroups and secondary endpoints. Real-world study data post-approval has largely not yet emerged for lefamulin, and there is a need for further investigation into safety/efficacy for off-label indications such as acute bacterial skin and skin structure infections (ABSSSIs) and sexually transmitted infections (STIs). Further data regarding tolerability, particularly with longer term use, as well as the emergence of resistance over time are still undefined. This article is protected by copyright. All rights reserved.

AIM End-to-end anastomosis staplers are frequently used in colorectal surgery, generating two anastomotic doughnuts. Whether pathological evaluation of the doughnut changes clinical practice remains unclear. We aim to identify any effects of pathological evaluation of anastomotic doughnuts after oncological colorectal surgery. METHOD We performed a systematic literature search utilizing PubMed, Clinicaltrials.gov, Cochrane, Embase and Web of Science databases and selected studies on evaluation of the anastomotic doughnut after oncological colorectal surgery with stapled end-to-end anastomosis. Outcome measures included: involved distal margin on the oncological sample, histological involvement of the doughnut, clinical change in management from a positive doughnut and study recommendations. RESULTS Of the 5761 studies identified, eight studies encompassing 1754 patients were evaluated. Most operations were for primary colon (37.5%) or rectal adenocarcinoma (37.5%). Incidence of distal margin involvement of the oncological sample was reported in three papers, with six positive cases (1.1%). Of the 1754 doughnut pairs evaluated, five were positive for neoplasia (0.29%), three for adenomas (0.18%) and one for metaplastic polyp (0.06%), none of which changed postoperative treatment. Four studies recommended abandoning routine histopathological evaluation of anastomotic doughnuts, while the remaining four recommended evaluation only under certain criteria, including gross distal margin

Background Community pharmacists can play a meaningful role in identification and treatment of substance use disorders (SUD). However, inadequate disease knowledge and negative attitudes are known barriers. The relationship between knowledge, attitudes, and practice of pharmacists regarding persons with SUD has not been evaluated comprehensively in the United States. The objective of the study was to assess knowledge of community pharmacists regarding medications for SUD and evaluate their attitudes, levels of stigma, and clinical practices in SUD. Methods A questionnaire was developed to assess practices, knowledge, screening services, and attitudes toward harm reduction strategies and treatment. A standardized measure of stigma was included along with demographics. A cross-sectional electronic survey was conducted in Pennsylvania, Ohio, and West Virginia among a non-probability sample of community pharmacists working for a retail pharmacy chain (n = 910) and a local alumni network ( n = 50). Scores were calculated for each factor and descriptive analyses, mean differences ( t-tests and ANOVA), correlations with demographics and practice characteristics were performed. Linear and ordinal regressions were utilized to predict knowledge, practice, screening, and stigma scores. Results A total of 134 responses (response rate 13.9%) were collected. On average, the pharmacists were 38 years old, had worked for 15 years, primarily full-time with practice locations in suburban settings. Only 53% reported they received SUD education in pharmacy school. Pharmacists received a mean score of 5.5 and 3.5 out of eight and seven on knowledge and practice scales, respectively. Pharmacists overall had slightly stigmatizing and negative attitudes, with higher stigma significantly related to performing lesser services and considering screenings as important. Number of years worked significantly predicted knowledge and screening. Conclusion Relationships between knowledge, attitudes, and practices indicate a need for experiential education that includes psychosocial aspects of care with increased opportunities for practice.

Objectives Iliac branch devices (IBDs) are modular, bifurcated endografts designed to preserve hypogastric flow during endovascular aortoiliac aneurysm repair. We report our single center outcomes, and describe the unique complications of these devices: inability to cannulate the hypogastric artery (technical failure), occlusion of the internal branch, and type III endoleak from separation of components between the main body and IBD. Methods A prospectively maintained institutional database of patients undergoing IBD implantation between 2014 and 2019 was reviewed. Technical and clinical outcomes were evaluated. We then identified patients having one of the IBD-specific complications and patient, anatomic, and procedural data were analyzed to identify factors associated with these failures. Results Sixty-four IBDs were placed in 59 patients during the study period. Mean age was 71.2 ± 8.6, and 92% were male. A 74.6% of patients had a current or prior abdominal aortic aneurysm, and 9.4% had a hypogastric aneurysm. Technical success was achieved in 60/64 cases (93.8%); prior endovascular aortic repair was associated with technical failure (P = 0.04). There were 5 instances of component separation between the main body and the IBD: 3 occurred intraoperatively and were repaired with additional bridging components, and 2 occurred on late follow-up and required reintervention. Increased tortuosity index of both aortoiliac (1.7 ± 0.4 vs. 1.3 ± 02, P = 0.04) and iliac-specific (3.9 ± 2.4 vs. 1.9 ± 0.9, P = 0.03) segments were significantly associated with component separation, as was the use of larger internal iliac components (13.9 ± 2.4 vs. 11.1 ± 2.3 mm, P = 0.04). Internal branch occlusions occurred in 4 patients (6.7%). Two were successfully reopened with endovascular procedures, with two being asymptomatic. No specific factors were found to be predictive of branch occlusion. Conclusions IBD-specific complications occur rarely. History of prior endovascular aortic repair is associated with technical failure, while increased aortic and iliac tortuosity are predictive of component separation and type III endoleak. Severe tortuosity should be carefully considered when planning for IBD.

Objective Hybrid lower extremity revascularization has been well described, typically consisting of common femoral endarterectomy (CFE) followed by direct patch puncture and endovascular treatment of any distal disease. We describe a modified technique that obviates the need for endovascular re-entry and simplifies treatment at the proximal and distal endpoints. Methods The REWIRE technique begins with retrograde arterial access via a patent tibial, pedal or femoropopliteal vessel. The diseased segment is crossed in the subintimal plane. Once the wire reaches the common femoral artery (CFA), the vessel is surgically exposed. Arteriotomy is performed and the wire is externalized during standard CFE. With through-wire access achieved, a sheath is inserted and the distal disease is treated. The proximal extent of the endovascular revascularization is incorporated into a standard CFE with patch angioplasty. Results Seven patients with chronic limb-threatening ischemia were treated with this approach, all with long segment occlusions of the SFA and significant CFA disease. The SFA disease was stented and bovine pericardial patch was used for CFE in all. Technical success was achieved in all patients. There were no complications related to the retrograde puncture site, which was controlled with manual pressure (4) or excluded with a covered stent (3). Thirty-Day freedom from major adverse limb events was 100%. Conclusions The REWIRE technique is an effective approach to hybrid revascularization involving the CFA. By crossing the occluded segment in a retrograde fashion and surgically externalizing the wire during CFE, the proximal and distal endpoints can be addressed with ease, the profunda femoris is protected under direct visualization, and the need for endovascular re-entry is eliminated.

PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

There is evidence of practice consolidation in US health care in recent years. To our knowledge, a detailed quantitative study of recent changes in radiation oncology practice size has not been performed. We aim to evaluate radiation oncology practice size changes between 2012 and 2020 in the United States.Using the Medicare Physician Compare Database, we identified practices employing radiation oncologists using their taxpayer identification number and individual radiation oncologists using their national provider identifier. We grouped individual radiation oncologists into categories by practice size (which includes the number of physicians of all specialties) and compared the number of radiation oncologists in each category between 2012 and 2020. Further analyses by US geographic census region, single-specialty practice, academic practice, and high- and low-population density areas were performed.Between 2012 and 2020, the total number of practicing radiation oncologists increased by 9%, and the number of practices employing radiation oncologists decreased by 11.5%. The number of radiation oncologists in practices of size 1 to 2, 3 to 9, 10 to 24, and 25 to 49 decreased by 3.7%, 4.7%, 4.9%, and 2%, respectively, and the number of radiation oncologists in practices of size 50 to 99, 100 to 499, and 500+ increased by 1.4%, 2.1%, and 11.8%, respectively (all 500+ practices are multispecialty groups). The increase in practice size was significant in all regions, for single-specialty and multispecialty practices, academic and nonacademic practices, and for practices in high-, middle-, and low-population density areas (P.05 for all comparisons). The proportion of single-specialty practices has decreased significantly (P.001), and the proportion of academic practices increased significantly (P = .004). Additionally, the proportion of practices and physicians in high- and low-population density regions remained stable during this period (P.05).Our analysis suggests that practice size consolidation has occurred within the US radiation oncology workforce from 2012 to 2020. The impact of this consolidation on quality, cost, and patient access deserves further attention.

Community pharmacists have significant opportunity to contribute to prevention and treatment of opioid use disorders, but barriers to implementation still exist. Understanding their viewpoints is critical to designing future interventions.To qualitatively explore experiences and beliefs of community pharmacists regarding the misuse of prescription opioids in the United States.The study was part of a larger project that utilized a survey questionnaire to evaluate the relationships between knowledge, attitudes, and practices of community pharmacists in substance use disorders. The survey included an open-ended item on pharmacist views regarding the prescription opioid epidemic. The responses were used for inductive content analysis. Axial coding of themes was conducted to analyze underlying relationships: associations, consequences, intervening relationships, and action strategies regarding a central phenomenon. A model describing pharmacist experiences in the opioid epidemic was conceptualized.The open-ended question resulted in 50 (37.3%) usable responses. Final abstraction resulted in six themes including (1) overprescribing opioids: inappropriate prescribing as a contributor to the epidemic, (2) policy and practice recommendations: potential action strategies against the epidemic, (3) poor prescriber-pharmacist relationship: barrier to addressing the epidemic, (4) negative attitudes: intervening condition affecting roles of the pharmacist, (5) personal experience: facilitator to improve pharmacist roles and (6) decreased access to opioids: consequence of strict prescribing laws.The study identified themes that described pharmacist views, attitudes, barriers, and experiences related to their perceived role in prevention and treatment of opioid use disorders. Future research should consider the implications of the barriers and facilitators identified.

Purpose To objectively identify the 50 most influential studies in knee arthroscopy and provide an analysis of their key characteristics. Methods The Clarivate Analytics Web of Knowledge database was used to gather data and metrics of knee arthroscopy research. The search list was sorted by the number of citations, and articles were included or excluded based on relevance to knee arthroscopy. The information extracted for each article included author name, publication year, country of origin, journal name, article type, and the level of evidence. Results For these 50 studies, the total number of citations was calculated to be 12,168, with an average of 243.4 citations per paper. The most-cited article was cited 1,220 times. The 50 studies included in this analysis were published between 1972 and 2013. All 50 articles were published in English and came from 10 different orthopaedic journals. The United States was responsible for the majority of articles (n = 26); however, many other countries were represented. The most prevalent study designs were case series (n = 20). Conclusions The 50 most influential articles in knee arthroscopy were cited a total of 12,168 times. The study designs most commonly used were case series and cohort studies. This article serves as a reference to direct orthopaedic practitioners to the 50 most influential studies in knee arthroscopy. We hope that these 50 studies and the analysis we provide help health care professionals efficiently assess consensus, trends, and needs within the field. Clinical Relevance This analysis of the 50 most influential studies in knee arthroscopy will provide medical students, residents, fellows, and attending physicians with a comprehensive inventory and citation analysis of the most impactful academic contributions to one of the most important fields within orthopaedic surgery.

Trochlear dysplasia (TD) is a key predisposing risk factor for patellar instability (PI) and lateral patellar dislocation (LPD) injuries. It is useful to understand the reliability of radiographic findings of TD and the accuracy of knee radiographs in diagnosing patients with recent LPD. The purposes of our study are to evaluate the inter-rater reliability of specific radiographic signs of PI and staging of TD between radiologists and orthopedic surgeons, and to identify which findings are associated with recent LPD. This retrospective study comprised 336 patients aged 8 to 18 who obtained knee radiographs over a 3-year period. Two radiologists and two orthopedic surgeons, blinded to patient history, examined radiographs for indicators of PI. Using data from 19 confirmed LPD cases and 317 controls, inter-observer agreement (kappa, Pearson’s correlation coefficient) was assessed, as was the odds ratio for likelihood of LPD. There was nearly perfect agreement between radiologists for patella-tendon ratios (Pearson’s correlation coefficient 0.8377, P

BACKGROUND Prurigo nodularis (PN) is associated with a variety of systemic comorbidities, including infectious diseases such as HIV and viral hepatitis. There are limited data on other infectious disease comorbidities in patients with PN. AIM To characterize infectious disease hospitalizations among patients with PN and the associated cost burden. METHODS We searched the 2016-2017 National Inpatient Sample, a cross-sectional sample of 20% of all US hospitalizations, for infectious disease hospitalizations among patients with PN. Associations of PN with infections and related costs were determined using multivariable logistic and linear regression, adjusting for age, race, sex and insurance type. RESULTS PN was associated with any infection overall (OR = 2.98, 95% CI 2.49-3.56), and with HIV, cutaneous, hepatobiliary, central nervous system, bacterial, viral and fungal/parasitic infections and for sepsis. Patients with PN had a higher mean cost of care (US$11 667 vs. US$8893, P

Thoracic endovascular aortic repair (TEVAR) is an effective treatment of blunt thoracic aortic injury (BTAI). However, the risks and benefits of administering intraoperative heparin in trauma patients are not well-defined, especially with regard to bleeding complications.The Vascular Quality Initiative registry was queried from 2013 to 2019 to identify patients who had undergone TEVAR for BTAI with or without the administration of intraoperative heparin. Univariate analyses were performed with the Student t test, Fisher exact test, or χA total of 655 patients were included, of whom most had presented with grade III (53.3%) or IV (20%) BTAI. Patients receiving heparin were less likely to have an injury severity score (ISS) of ≥15 (70.2% vs 90.5%; P .0001) or major head or neck injury (39.6% vs 62.9%; P .0001). Patients receiving heparin also had a lower incidence of inpatient death (5.1% vs 12.9%; P .01). Across all injury grades, heparin use was not associated with the need for intraoperative transfusion or postoperative transfusion or the development of hematoma. In patients with grade III BTAI, the nonuse of heparin was associated with an increased risk of lower extremity embolization events (7.4% vs 1.8%; P .05). On multivariable logistic regression analysis for inpatient mortality, intraoperative heparin use (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.86; P .05) and female gender (OR, 0.11; 95% CI, 0.11-0.86; P .05) were associated with better survival, even after controlling for head and neck trauma and injury grade. In contrast, increased age (OR, 1.06; 95% CI, 1.03-1.1; P .001), postoperative transfusion (OR, 1.06; 95% CI, 1.02-1.11; P .01), higher ISS (OR, 1.04; 95% CI, 1.01-1.07; P .05), postoperative dysrhythmia (OR, 4.48; 95% CI, 1.10-18.18; P .05), and postoperative stroke or transient ischemic attack (OR, 5.54; 95% CI, 1.11-27.67; P .05) were associated with increased odds of inpatient mortality.Intraoperative heparin use was associated with reduced inpatient mortality for patients undergoing TEVAR for BTAI, including those with major head or neck trauma and high ISSs. Heparin use did not increase the risk of hemorrhagic complications across all injury grades. Also, in patients with grade III BTAI, heparin use was associated with a reduced risk of lower extremity embolic events. Heparin appears to be safe during TEVAR for BTAI and should be administered when no specific contraindication exists.

Dyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia., Diverse macrophage subsets are found in adipose tissue where they regulate its physiology. Here, the authors used single-cell RNA sequencing to analyse the effect of post-prandial lipids on adipose tissue macrophages and identify Tim4 as a regulator of ABCA1+ macrophage function and post-prandial cholesterol transport.

Introduction The purpose of this study was to evaluate trends in annual arthroplasty volume among the Medicare population, as well as assess true Medicare reimbursement to physicians for all hip and knee arthroplasty procedures billed to Medicare since year 2000. Methods The publicly available Medicare Part B National Summary Data File from years 2000 to 2019 was utilized. Collected data included true physician reimbursements for all primary total hip and knee, unicompartmental knee, and revision hip/knee arthroplasty procedures from 2000 to 2019. Monetary data was adjusted for inflation to year 2019 dollars. Change was assessed and compared by procedure type. Results From 2000 to 2019, physicians billed Medicare Fee-For-Service for 8,363,821 hip and knee arthroplasty procedures. During this time, the annual number of included arthroplasty procedures billed to Medicare increased by 100%. From 2000 to 2019 across all included procedures, the mean physician reimbursement after adjusting for inflation decreased by -$729.82 (-38.9%) per procedure. This varied by procedure type. Unicompartmental knee arthroplasty was the only procedure to experience an increased mean reimbursement when adjusting for inflation, increasing by $241.40 (+16.6%) per procedure from 2000 to 2019. Conclusion This study demonstrates decreasing Medicare reimbursement to physicians within hip and knee arthroplasty from 2000 to 2019 when adjusting for inflation. This study is important for informing the potential development of more equitable payment models and maintaining access for arthroplasty care moving forward.

BackgroundDiffuse intrinsic pontine gliomas (DIPG) generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR).MethodsPatients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included. The primary outcome was overall survival (OS) categorized as long-term survivors (LTS) (≥24 months) or short-term survivors (STS) (ResultsAmong 1010 patients, 208 (21%) were ≥10 years of age at diagnosis; 152 were eligible with a median age of 12 years (range 10-26.8). Median OS was 13 (2-82) months. The 1-, 3-, and 5-year OS was 59.2%, 5.3%, and 3.3%, respectively. The 18/152 (11.8%) LTS were more likely to be older (P < .01) and present with longer symptom duration (P < .01). Biopsy and/or autopsy were performed in 50 (33%) patients; 77%, 61%, 33%, and 6% of patients tested had H3K27M (H3F3A or HIST1H3B), TP53, ATRX, and ACVR1 mutations/genome alterations, respectively. Two of 18 patients with IDH1 testing were IDH1-mutant and 1 was a LTS. The presence or absence of H3 alterations did not affect survival.ConclusionPatients ≥10 years old with DIPG have a median survival of 13 months. LTS present with longer symptom duration and are likely to be older at presentation compared to STS. ATRX mutation rates were higher in this population than the general DIPG population.

Children with low-grade gliomas have excellent long-term survival outcomes. The development of therapies targeted to the driver mutations along the Mitogen Activated Protein (MAP) kinase signalling pathway are providing long-term stability for many patients with these tumours. Given the frequency of these tumours residing within or near the suprasellar region, our patients commonly suffer from hormone deficiencies. In Australia, the Pharmaceutical Benefits Scheme currently restricts growth hormone therapy to patients who are not being actively treated for cancer, including those receiving targeted therapies. This viewpoint hopes to facilitate an important discussion amongst our colleagues as to whether this should be changed to allow growth hormone to become available to children on chronic tumour suppressive therapy.

Introduction A growing body of scientific evidence points to the potentially harmful cognitive effects of anticholinergic medications among older adults. Most interventions designed to promote deprescribing of anticholinergics have directly targeted healthcare professionals and have had mixed results. Consumer-facing technologies may provide a unique benefit by empowering patients and can complement existing healthcare professional-centric efforts. Methods We initiated a randomized clinical trial to evaluate the effectiveness of a patient-facing mobile application (Brain Safe app) compared to an attention control medication list app in reducing anticholinergic exposure among community-dwelling older adults. Study participants are adults aged 60 years and above, currently using at least one prescribed strong anticholinergic, and receiving primary care. The trial plans to enroll a total of 700 participants, randomly allocated in 1:1 proportion to the two study arms. Participants will have the Brain Safe app (intervention arm) or attention control medication list app (control arm) loaded onto a smartphone (study provided or personal device). All participants will be followed for 12 months and will have data collected at baseline, at 6 months, and 12 months by blinded outcome assessors. The primary outcome of the study is anticholinergic exposure measured as total standard daily dose (TSDD) computed from medication prescription electronic records. Secondary outcomes of the study are cognitive function and health-related quality of life. Discussion A consumer-facing intervention to promote deprescribing of potentially high-risk medications can be part of a multi-pronged approach to reduce inappropriate medication use among older adult patients. Delivering a deprescribing intervention via a mobile app is a novel approach and may hold great promise to accelerate deployment of medication safety initiatives across diverse patient populations. Clinical trial registration Registered at ClinicalTrials.gov on October 10, 2019. Identifier number: NCT04121858.

Background: Total shoulder arthroplasty (TSA) has increased in utilization over the past several decades. Anemia is a common preoperative condition among patients undergoing TSA and has been associated with poorer outcomes in other surgical procedures. To the best of our knowledge, no study has analyzed the association between anemia severity and TSA outcomes. Therefore, the purpose of this study is to determine the effects that increasing severity of anemia may have on the postoperative outcomes in patients receiving primary TSA. Methods: A retrospective analysis was performed using the American College of Surgeons National Surgery Quality Improvement Project database from the years 2015 to 2018. Current Procedure Terminology code 23472 was used to identify all primary TSA procedures recorded during this time frame. Patients with greater than 38% preoperative hematocrit (HCT) were classified as having normal HCT levels. Patients with HCT values between 33% and 38% were classified as having mild anemia. All patients with less than 33% HCT were classified as having moderate/severe anemia. Patient demographic information, preoperative risk factors, and postoperative outcomes were compared among the 3 cohorts. A multivariate logistic regression including demographic factors and comorbidities was performed to determine whether increasing severity of anemia is independently associated with poorer postoperative outcomes. Results: Of the 15,185 patients included in this study, 11,404 had normal HCT levels, 2962 patients were mildly anemic, and 819 patients had moderate to severe anemia. With increasing severity of anemia, there was an increased average hospital length of stay (1.6 vs. 2.1 vs. 3.0 days, P

Opioids are one of the most prescribed classes of analgesic medications. Their narrow therapeutic index and metabolism through cytochrome p450 (CYP) enzymes can result in a drug interaction when used concomitantly with rifamycins. In clinical scenarios where concurrent therapy with an opioid and a rifamycin occurs, there is no standardized guidance for managing the interaction. The objective of this review was to examine literature which evaluates the concomitant use of opioids and rifamycins with clinically relevant CYP-inducing properties. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria was performed. PubMed, Scopus, and OVID Embase were queried for studies from database inception to January 2020 related to rifamycin and opioid medications. Only full-text, peer-reviewed, English language articles addressing clinical outcomes from concomitant rifamycin and opioid therapy were included. The review isolated 12 articles for data extraction from an original 2260 citations identified. Rifampin (11; 92%) and rifabutin (2; 17%) were the rifamycins studied along with seven different opioids. Decreased effect of opioids with concomitant rifampin therapy manifested as withdrawal in numerous patients on methadone and a decreased analgesic effect from tramadol, morphine, and, most notably, oxycodone. Only the combinations of rifampin with buccal fentanyl and rifabutin with buprenorphine and methadone were found to have no clinically measurable interaction. Available literature suggests that a decrease in opioid clinical effects is appreciated with concomitant rifamycin therapy. Further research is needed to focus on specific mitigation strategies beyond opioid agent selection, such as dosing adjustment recommendations.

Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against use in patients with a BMI > 40 kg/m2 or bodyweight > 120 kg unless drug-specific levels are measured, which may not be feasible across all clinical practices. Accordingly, the objective of this study was to broadly examine literature evaluating the clinical outcomes of rivaroxaban and/or apixaban in patients with increased body mass. A systematic literature review (guided by PRISMA) was performed through January 27, 2021 using PubMed, Embase, and Scopus. Key search term clusters included drug and weight-related concepts (overweight/obese, body mass index [BMI], waist circumference). DistillerSR was utilized to review and process search results. Studies met inclusion if they analyzed the risk of bleeding and/or thrombosis in patients with increased body mass (i.e., via BMI or other criteria) receiving rivaroxaban or apixaban. Clinical guidelines, case reports/series, pharmacokinetic/dynamic analyses, and commentaries were excluded. Bias was examined qualitatively across studies. After duplicates were removed, the original search rendered 1822 abstracts and 200 full-texts for screening, ultimately providing a final set of 24 studies for qualitative review. Of these studies, 13 (54.2%) enabled comparisons between patients of increased versus normal body mass, while 11 (45.8%) reported outcomes only for patients of increased body mass. The working definition of ‘increased body mass’ varied amongst the studies, including 11 (45.8%) studies that utilized BMI, seven (29.2%) with a combination of BMI and body measurement, two (8.3%) that relied on body weight alone, and four (16.7%) that identified obesity-related ICD codes. All 13 comparative studies found similar or reduced rates of safety and efficacy outcomes with rivaroxaban and apixaban. The literature reports similar or lower bleeding and thrombotic risk for rivaroxaban and apixaban in patients of increased body mass compared to patients of normal body mass. Future prospective controlled studies are needed to further define guidelines for use in this population.

BackgroundRecent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked power to integrate molecular and clinical findings. The different proposed subgroup structures also highlighted a need to reach consensus on a robust and relevant classification system.MethodsWe performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical and genomic features of patients and samples from these pineal tumor subgroups were annotated.FindingsFour clinically and biologically relevant consensus PB subgroups were defined: PB-miRNA1 (n=96), PB-miRNA2 (n=23), PB-MYC/FOXR2 (n=34) and PB-RB1 (n=25); with PPTID (n=43) remaining as a molecularly distinct entity. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual subgroups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection and metastatic status varied significantly among tumor subgroups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 and PB-RB1.InterpretationWe systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease subgroups, laying the groundwork for future studies as well as routine use in tumor classification.

Purpose To determine the 50 most frequently cited studies in the orthopaedic shoulder arthroscopy literature and to conduct a bibliometric analysis of these studies. Methods The Clarivate Analytics Web of Knowledge database was used to gather data and metrics using Boolean queries to capture all possible iterations of shoulder arthroscopy research. The search list was sorted so that articles were organized in descending order based on the number of citations and included or excluded based on relevance to shoulder arthroscopy. The information extracted for each article included author name, publication year, country of origin, journal name, article type, and the level of evidence. Results For these 50 studies, the total number of citations was calculated to be 13,910, with an average of 278.2 citations per paper. The most-cited article was cited 1134 times, whereas the second- and third-most cited articles were cited 920 and 745 times, respectively. All 50 articles were published in English and came from 7 different orthopaedic journals. The United States was responsible for most of the included articles (31), followed by France (9) and Japan (3). Conclusions The majority of the most-cited articles in shoulder arthroscopy are case series and descriptive studies originating from the United States. In addition, more than one half of the top 50 most-cited studies were published after 2004, which suggests that article age may be less important in the accumulation of citations for a rapidly growing field like shoulder arthroscopy. Clinical Relevance The top 50 most-cited studies list will provide researchers, medical students, residents, and fellows with a foundational list of the most important and influential academic contributions to shoulder arthroscopy.

A massive localized trauma to the spinal cord results in complex pathologic events driven by necrosis and vascular damage which in turn leads to hemorrhage and edema. Severe, destructive and very protracted inflammatory response is characterized by infiltration by phagocytic macrophages of a site of injury which is converted into a cavity of injury (COI) surrounded by astroglial reaction mounted by the spinal cord. The tissue response to the spinal cord injury (SCI) has been poorly understood but the final outcome appears to be a mature syrinx filled with the cerebrospinal fluid with related neural tissue loss and permanent neurologic deficits. This paper reviews known pathologic mechanisms involved in the formation of the COI after SCI and discusses the integrative role of reactive astrogliosis in mechanisms involved in the removal of edema after the injury. A large proportion of edema fluid originating from the trauma and then from vasogenic edema related to persistent severe inflammation, may be moved into the COI in an active process involving astrogliosis and specifically over-expressed aquaporins.

Objective:To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics.Design:Retrospective, observational, cross-sectional study.Setting:Hospitals in the southeastern United States.Methods:AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum β-lactamase (ESBL)–producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal β-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared.Results:Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016.Conclusions:The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.

PurposePerceptual judgments of articulatory function are commonly used by speech-language pathologists to evaluate articulatory performance in individuals with amyotrophic lateral sclerosis (ALS). The goal of this study was to evaluate the psychometric properties (e.g., reliability, validity) of these perceptual measures to inform their application as part of a comprehensive bulbar assessment tool in ALS.MethodPreexisting data from 51 individuals with ALS were obtained from a larger longitudinal study. Five independent raters provided perceptual judgments of articulatory rate and imprecision in a sentence task. Inter- and intrarater reliability of these judgments were assessed. Perceptual ratings were correlated with an acoustic measure of articulatory rate, in syllables per second, obtained from passage-reading recordings. Both perceptual and acoustic measures were correlated with gold-standard kinematic tongue and jaw movement measures, recorded from sentences using electromagnetic articulography.ResultsThe results revealed good inter- and intrarater reliability of perceptual judgments of articulatory function. Strong correlations were observed between perceptual ratings of articulatory rate and imprecision and acoustic measures of articulatory rate and kinematic measures of tongue speed.ConclusionsThese findings support the clinical application of perceptual judgments of articulatory function as valid and reliable measures of underlying articulatory changes in bulbar ALS. Additional research is needed to understand the responsiveness of these measures to clinical changes in articulatory function in ALS.

Background Reports of gabapentinoid (gabapentin and pregabalin) misuse are on the rise, but few studies have assessed this within the general US population. Objective Describe lifetime misuse/abuse/non-prescribed obtainment of gabapentinoids and descriptive characteristics associated with such actions in a US general population sample. Setting This cross-sectional questionnaire was administered online by Qualtrics® research panel aggregator via quota-based sampling. Methods Data were collected from a sample of respondents that mirrored the general US population aged 18–59 years with regards to age, geographic region, ethnicity, income, and education level, based on most recent census data. Misuse/abuse/non-prescribed obtainment was collectively defined as use of a gabapentinoid for reasons other than a diagnosed medical condition, using with the intention of altering one’s state of consciousness, or obtaining without a prescription. A multivariable logistic regression model was created to predict misuse/abuse/non-prescribed obtainment of gabapentinoids, incorporating relevant covariates. Main outcome measure Proportion of sample indicating lifetime misuse/abuse/non-prescribed obtainment of gabapentinoids. Results Among 1,843 respondents, 121 (6.6%) reported gabapentinoid misuse/abuse/non-prescribed obtainment. Specifically, 2.1% (n = 39) and 1.5% (n = 27) of respondents for gabapentin and pregabalin, respectively, met study criteria for abuse. Opioids were the most common medication co-administered with gabapentinoids (among 50–70% of respondents) for misuse/abuse. Previous treatment for addiction (OR: 2.61, 95% CI: 1.32–5.14, p = 0.005) and the total attitudinal risk score (OR: 1.14, 95% CI: 1.09–1.19, p

A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially. Update previous SR and describe new insights regarding gabapentinoid abuse. A SR of PubMed was conducted to identify studies published from 7/29/2016–8/31/2020. Four searches were performed using the following terms: “gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid” AND one of the following substance misuse/abuse-related terms: “substance-related disorders [MeSH]”, “overdose”, “abuse”, or “misuse”. Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded. Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid-related overdose mortality risk. Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.

Study objective The change in reimbursement rates for emergency physician services has yet to be quantified. We attempted to fill this knowledge gap by evaluating the monetary trends in Medicare reimbursement rates over the last 20 years for the most common emergency medicine services. Methods We obtained commonly used Current Procedural Terminology (CPT) codes in emergency medicine from the American College of Emergency Physicians website. We queried the Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services for each of the included CPT codes, and we extracted reimbursement data. We adjusted all monetary data for inflation to 2020 US dollars by using changes to the United States consumer price index. Both the average annual and the total percentage change in reimbursement were calculated on the basis of these adjusted trends for all included services. Results Reimbursement by Medicare for the services decreased by an average of 29.13% from 2000 to 2020 after adjusting for inflation. There was a stable decline in adjusted reimbursement rates throughout the study period, with an average decrease of 1.61% each year. The largest decrease was seen for laceration repairs up to 7.5 cm, with reimbursement rates for all 4 relevant CPT codes decreasing by more than 60%. Conclusion When adjusted for inflation, Medicare reimbursement declined by an average of 29% over the last 20 years for the 20 most common emergency medicine services. Knowledge of these trends is essential to address current controversies in emergency medicine billing adequately and advocate for sustainable payment system reform.

Purpose Clear guidelines are needed for the inclusion of transgender voice and communication services in speech-language pathology graduate curriculum. Standardized training on how to support gender diverse individuals' communication appears to be lacking in graduate curriculum. To better understand current trends in transgender voice and communication training in speech-language pathology graduate programs across the United States, this cross-sequential e-survey study assessed experience with, attitudes toward, and student learning opportunities in transgender voice and communication services among voice instructors and clinic directors. Method An open online survey distributed in 2015 was completed by 24 voice instructors and 13 clinic directors. The same survey was completed by 15 voice instructors in 2018. Results Based on 2015 findings, a majority of voice instructors and clinic directors in speech-language pathology graduate programs reported that services for transgender voice and communication were not addressed in their graduate education curriculum. Findings from 2018 were similar to results in 2015. Almost all voice instructors included transgender voice and communication therapy in their graduate voice course. There is unanimous agreement that transgender voice and communication services should be part of SLPs' scope of practice. Conclusions Findings from 2015 to 2018 suggested an improvement in instruction time spent on transgender voice and communication. Yet, some voice instructors continued to report that the topic was not covered in their coursework. A need exists to adjust guidelines on voice and communication services for gender diverse individuals and offer learning opportunities for this area in graduate speech-language pathology curriculum. Supplemental Material https://doi.org/10.23641/asha.12640409

The impact of resecting positive margins during pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDA) remains debated. Additionally, the survival benefit of resecting multiple positive margins is unknown. We identified patients with PDA who underwent PD from 2006 to 2015. Pancreatic neck, bile duct, and uncinate frozen section margins were assessed before and after resection of positive margins. Survival curves were compared with log-rank tests. Multivariable Cox regression assessed the effect of margin status on overall survival. Of 501 patients identified, 17.3%, 5.3%, and 19.7% had an initially positive uncinate, bile duct, or neck margin, respectively. Among initially positive bile duct and neck margins, 77.8% and 67.0% were resected, respectively. Although median survival was decreased among patients with any positive margins (15.6 vs. 20.9 months; p = 0.006), it was similar among patients with positive bile duct or neck margins with or without R1 to R0 resection (17.0 vs. 15.6 months; p = 0.20). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p = 0.04). Uncinate margins were never resected. Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p = 0.37). Patients with positive margins who received adjuvant therapy had improved survival, regardless of margin resection (p = 0.03). Adjuvant therapy was independently protective against death (hazard ratio 0.6, 95% CI 0.5–0.7). Positive PD margins at any position are associated with reduced overall survival; however, resection of additional margins may not improve survival, particularly with concurrently positive uncinate margins. Adjuvant chemotherapy improves survival with positive margins, regardless of resection.

Ultrasound-enhanced catheter-directed thrombolysis (UET) using the Ekosonic® Endovascular System device for acute, peripheral arterial ischemia has been purported in clinical trials to accelerate the fibrinolytic process to reduce treatment time and lytic dosage. We aim to describe outcomes of UET in a real-world clinical setting.We performed a retrospective review of all patients undergoing UET for acute limb ischemia at a single institution. Data collected included patient demographics, procedural details, and 30-day and 1-year outcomes. The primary endpoints for analysis were major adverse limb events (MALEs; reintervention and/or amputation) and mortality within 30-days and 1-year. Secondary endpoints included technical success, use of adjunctive therapies, and postoperative complications.A total of 32 patients (mean age 67.4 ± 14.9 years; 25% women) underwent UET for acute limb ischemia between 2014 and 2018. The Rutherford Acute Limb Ischemia Classification was Rutherford (R) 1 in 56.3%, R2a in 31.3%, and R2b in 12.5%. Etiology was thrombosis of native artery in 12.5% of patients, prosthetic bypass in 31.3%, autogenous bypass in 6.3%, and stented native vessel in 50.0%. Mean duration of thrombolytic therapy was 22.2 ± 11.3 hr, and mean tissue plasminogen activator dose was 24.5 ± 15.3 mg. MALEs occurred in 16.7% of patients within the first 30 days and 38.9% experienced a MALE by 1 year. Limb salvage at 30 days and 1 year was 93.8% and 87.5%, respectively. Ipsilateral reintervention was required in 12.5% of patients within 30 days and 37.5% of patients within 1 year. Overall mortality was 6.2% at 30 days and 13.5% at 1 year. In-line flow to the foot was re-established in 90.6% of patients, with a significant improvement in preoperative to postoperative ankle-brachial index (0.31 ± 0.29 vs. 0.78 ± 0.34, P 0.001) and number of patent tibial runoff vessels (1.31 ± 1.20 vs. 1.96 ± 0.86, P 0.001). There was no significant difference in revascularization success between occluded vessel types. All but one patient required adjunctive therapy such as further thromboaspiration, stenting, or balloon angioplasty. Major bleeding complications occurred in 3 patients (9.4%), including 1 intracranial hemorrhage (3.1%).UET with the EKOS device demonstrates acceptable real-world outcomes in the treatment of acute limb ischemia. UET is generally safe and effective at re-establishing in-line flow to yield high limb salvage rates. However, UET is associated with a high rate of reintervention. Further investigation is needed into specific predictors of limb salvage and need for reintervention, as well as cost-efficacy of this technology compared with that of traditional methods.

Objective.Early diagnosis of systemic sclerosis (SSc) is imperative, and Raynaud phenomenon (RP) is an important component of progressive vasculopathy. Nailfold videocapillaroscopy (NVC) is a well-established tool that can quantify structural vascular abnormalities. Digital thermal monitoring (DTM) assesses microvascular functional dysfunction related to thermoregulation. In this study, we investigated the correlation of NVC patterns and DTM variables in patients with SSc.Methods.Patients with SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism criteria who consented and enrolled in the clinical care registry had NVC and DTM performed. For NVC, the number of capillaries (density), measurement of apical diameter (dimension), presence or absence of hemorrhages, and number of abnormal shapes were assessed to categorize 3 different qualitative patterns: early, active, and late. For DTM, Doppler ultrasound hyperemic, low frequency, blood velocity of radial artery, and fingertip vascular function were assessed, and a vascular reactivity index (VRI) measurement was automated. Statistical evaluation was performed by nonparametric tests to assess the correlation of NVC and VRI.Results.Thirty-one SSc subjects with interpretable NVC and DTM performed on the same day were included in the study. VRI was progressively higher in SSc patients with early, active, and late NVC patterns of microangiopathy (P < 0.0001). There was a significant negative correlation between VRI and microhemorrhages scores (r = –0.363, P = 0.044).Conclusion.Our study suggests that more advanced vasculopathy correlates to reduced microvascular function as detected by DTM and more advanced structural abnormalities detected by NVC. NVC and DTM may provide different aspects of vasculopathy quantification and complement each other as investigative tools.

COVID-19 has wreaked havoc on the lives of persons around the world and social scientists are just beginning to understand its consequences on human behavior. One policy that public health officials put in place to help stop the spread of the virus were stay-at-home/shelter-in-place lockdown-style orders. While designed to protect people from the coronavirus, one potential and unintended consequence of such orders could be an increase in domestic violence – including abuse of partners, elders or children. Stay-at-home orders result in perpetrators and victims being confined in close quarters for long periods of time. In this study, we use data from Dallas, Texas to examine the extent to which a local order was associated with an increase in domestic violence. Our results provide some evidence for a short-term spike in the 2 weeks after the lockdown was instituted but a decrease thereafter. We note that it is difficult to determine just how much the lockdown was the cause of this increase as the domestic violence trend was increasing prior to the order.

Abtract Background This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR). Methods Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed. Results On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers. Conclusions Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.

Despite its recognized value, there is a gap in the assessment of patient satisfaction among patients with substance use disorder (SUD) in rehabilitation. The study objective was to determine patient satisfaction dimensions relevant to individuals receiving residential rehabilitation for SUD. Semi-structured interviews were conducted with the following: (1) adult males enrolled in the program and (2) counseling staff involved in the care of these individuals. A literature review formed the basis for interviews, which were audio recorded and transcribed. Text data was analyzed using directed content analysis to identify dimensions relevant to patient satisfaction. Eighteen individuals participated, including 14 men with SUD and four staff. Content analysis of the interview transcripts resulted in five themes: (1) counselor (skill), (2) programmatic structure (adhering), (3) skill development (personal responsibility), (4) comparison to other programs, and (5) case management facilitation. These dimensions will be utilized to create a patient satisfaction tool specific to SUD rehabilitation.

Objectives The superficial femoral artery can be used as inflow for infra-geniculate bypass, but progressive proximal occlusive disease may affect graft durability. We sought to evaluate the effect of superficial femoral artery versus common femoral artery inflow on infra-geniculate bypass patency within a large contemporary multicenter registry. Methods The vascular quality initiative was queried from 2013 to 2019 to identify patients with >30-day patency follow-up, Rutherford chronic limb ischemia stage 1–6, and an infra-geniculate bypass, excluding those with prior ipsilateral bypass. The cohort was stratified by inflow vessel, with primary, primary-assisted, and secondary patency serving as the primary outcome variables. Multivariate Cox-proportional hazard models and radius-based propensity-score matching were performed to reduce treatment-selection bias due to clinical covariates. Results A total of 11,190 bypass procedures were performed (8378 common femoral artery inflow, 2812 superficial femoral artery) on 10,110 patients, with a mean follow-up of 12.8 months (range 1–98). Patients receiving superficial femoral artery inflow bypasses were more commonly male ( p = 0.002), obese ( p Conclusions Within the vascular quality initiative, there is no significant difference in life-table determined three-year primary, primary-assisted, and secondary patency between infra-geniculate bypasses using common femoral artery inflow compared to superficial femoral artery inflow. Small, statistically significant differences exist in primary, primary-assisted, and secondary patency favoring common femoral artery inflow after propensity score matching. Long-term follow-up data are required in the vascular quality initiative to better evaluate bypass graft durability as this study was limited by a mean follow-up of one year.

Purpose: The neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation that has been investigated as a prognostic factor in many diseases. We hypothesized that NLR would be lower in patients undergoing minimally invasive distal pancreatectomy (MIDP). Methods: Using a prospective database, we identified patients who underwent open or minimally invasive (laparoscopic/robotic) distal pancreatectomy and splenectomy from 2006 to 2018. Patients were grouped according to their type of surgery and matched by age, gender, and benign or malignant pathology. The NLR was calculated from a complete blood count with differential on the second postoperative day. Statistical calculations were performed in Stata (v13.0). Results: A total of 106 patients were included, with 53 MIDP and 53 open cases. MIDP was associated with a significantly lower postoperative NLR than open surgery (13.3 vs. 17.2, p = 0.01). NLR did not vary significantly between patients who developed complications and those who did not (15.4 vs. 15.3, p = 0.95). Patients undergoing MIDP had decreased length of postoperative hospital stay (4 days vs. 5 days, p = 0.003). Multivariable linear regression failed to find a significant decrease in NLR with the use of laparoscopy (p = 0.14) when accounting for age, body mass index, surgical blood loss, pathology, and operative time as covariates. Conclusion: The NLR is significantly decreased when performing MIDP versus open distal pancreatectomy, but correlation with clinical outcomes has yet to be proven.

To evaluate the impact of an ambulatory clinical pharmacy service (inclusive of immunization needs assessments) on the frequency and appropriateness of pneumococcal vaccine administration in a family medicine clinic.This cohort study had an observational and retrospective design and included patients who received pneumococcal vaccines at a family medicine clinic in a medically underserved area in Southwestern Pennsylvania across a 42-month period from January 1, 2015, to June 30, 2018. The outcome measures included the administration and appropriateness of pneumococcal 13-valent conjugate (PCV13) and pneumococcal 23-valent polysaccharide (PPSV23) vaccines across 3 time cohorts including before, during, and after the establishment of a clinical pharmacy service.A total of 457 pneumococcal vaccines were administered, including 198 (43.3%) PCV13 and 259 (56.7%) PPSV23, across all time cohorts. Overall vaccine administration per month increased by 143% with the introduction of a dedicated clinical pharmacy service, including a 270% increase for PCV13 and an 87% increase for PPSV23. A strong correlation was found between recommendations made and doses administered for both pneumococcal vaccines (r = 0.89; P0.003). Across the entire time frame, PPSV23 administrations were appropriate in more than 96% of instances, whereas the appropriateness of PCV13 administrations were statistically significantly improved after the introduction of a fully dedicated clinical pharmacy service (58.5% vs. 90.8%; P0.05). The appropriateness of vaccine administration remained high even after the reduction of clinical pharmacy services.Clinical pharmacy service implementation in a family medicine clinic was associated with increased pneumococcal vaccine administration and increased appropriateness of PCV13 administrations.