Narcotic prescribing practices in shoulder surgery before and after the institution of narcotic e-prescribing.

Background: Given the current opioid epidemic, it is crucial to highly regulate the prescription of narcotic medications for pain management. The use of electronic prescriptions (e-scripts) through the hospital's electronic medical record platform allows physicians to fill opioid prescriptions in smaller doses, potentially limiting the total quantity of analgesics patients have access to and decreasing the potential for substance misuse. The purpose of this study is to determine how the implementation of e-scripts changed the quantity of opioids prescribed following shoulder surgeries. Methods: For this single-center retrospective study, data were extracted for all patients aged 18 years or more who received a shoulder procedure between January 2015 and December 2020. Total milligrams of morphine equivalents (MMEs) of opioids prescribed within the 90 days following surgery were compared between 3 cohorts: preimplementation of the 2017 New Jersey Opioid laws (Pre-NJ opioid laws), post-NJ Opioid Laws but pre-escripting, and postimplementation of e-scripting in 2019 (postescripting). Any patient prescribed preoperative opioids, prescribed opioids by nonorthopedic physicians, under the care of a pain management physician, or had a simultaneous nonshoulder procedure was excluded from this study. Results: There were 1857 subjects included in this study; 796 pre-NJ opioid laws, 520 post-NJ opioid laws, pre-escripting, and 541 postescripting. Following implementation of e-scripting on July 1, 2019, there was a significant decrease in total MMEs prescribed (P < .001) from a median of 90 MME (interquartile range 65, 65-130) preimplementation to a median 45 MME (interquartile range 45, 45-90) MME postimplementation Additionally, there was a statistically significant decrease in opioids prescribed for all procedures (P < .001) and for 3 (P < .001) of the 4 orthopedic surgeons included in this study. Conclusion: Our study demonstrated a significant reduction in total MMEs prescribed overall, for all shoulder surgeries, and for the majority of our institution's providers in the postoperative period following the e-scripting implementation in July 2019. E-scripting is a valuable tool in conjunction with education and awareness on the national, institutional, provider, and patient levels to combat the opioid epidemic.

American College of Lifestyle Medicine Expert Consensus Statement: Lifestyle Medicine for Optimal Outcomes in Primary Care.

OBJECTIVE: Identify areas of consensus on integrating lifestyle medicine (LM) into primary care to achieve optimal outcomes. METHODS: Experts in both LM and primary care followed an a priori protocol for developing consensus statements. Using an iterative, online process, panel members expressed levels of agreement with statements, resulting in classification as consensus, near consensus, or no consensus. RESULTS: The panel identified 124 candidate statements addressing: (1) Integration into Primary Care, (2) Delivery Models, (3) Provider Education, (4) Evidence-base for LM, (5) Vital Signs, (6) Treatment, (7) Resource Referral and Reimbursement, (8) Patient, Family, and Community Involvement; Shared Decision-Making, (9) Social Determinants of Health and Health Equity, and (10) Barriers to LM. After three iterations of an online Delphi survey, statement revisions, and removal of duplicative statements, 65 statements met criteria for consensus, 24 for near consensus, and 35 for no consensus. Consensus was reached on key topics that included LM being recognized as an essential component of primary care in patients of all ages, including LM as a foundational element of health professional education. CONCLUSION: The practice of LM in primary care can be strengthened by applying these statements to improve quality of care, inform policy, and identify areas for future research.

Disparities in arthroplasty utilization for rotator cuff tear arthropathy.

BACKGROUND: Rotator cuff tear arthropathy (CTA) carries a significant symptomatic burden for patients. Reverse shoulder arthroplasty (RSA) is an effective treatment intervention for CTA. Disparities in musculoskeletal medicine are well documented; however, there is a paucity of literature on how social determinants of health affect utilization rates. The purpose of this study is to determine how social determinants of health affect the utilization rates of RSA. METHODS: A single-center retrospective review was conducted for adult patients diagnosed with CTA between 2015 and 2020. Patients were divided by those who underwent RSA and those who were offered RSA but did not undergo surgery. Each patient's zip code was used to determine the most specific median household income in the US Census Bureau database and compared to the multistate metropolitan statistical area median income. Income levels were defined by the US Department of Housing and Urban Development's (HUD's) 2022 Income Limits Documentation System and the Federal Reserve's (FED's) Community Reinvestment Act. Because of numeric restrictions, patients were grouped into racial cohorts of Black, White, and all other races. RESULTS: Patients of other races had significantly lower odds of continuing to surgery compared with White patients in models controlled for median household income (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.18-0.81, P = .01), HUD's 3 income levels (OR 0.36, 95% CI 0.18-0.74, P = .01), and FED's income levels (OR 0.37, 95% CI 0.17-0.79, P = .01). There was no significantly different odds of going on to surgery between FED income levels and median household income levels, but when compared with those with low HUD income, those below median had significantly lower odds of going on to surgery (OR 0.43, 95% CI 0.23-0.80, P = .01). CONCLUSION: Although contradictory to reported health care utilization for Black patients, our study supports reported disparities in utilization for other ethnic minorities. These findings may suggest that improvements in utilization efforts targeted Black-identifying patients but not necessarily other ethnic minorities. The findings of this study can help providers understand how social determinants of health play a role in the utilization of care for CTA and direct mitigation efforts to reduce disparities in access to adequate orthopedic care.

Förster resonance energy transfer biosensors for fluorescence and time-gated luminescence analysis of rac1 activity.

Genetically encoded, Förster resonance energy transfer (FRET) biosensors enable live-cell optical imaging of signaling molecules. Small conformational changes often limit the dynamic range of biosensors that combine fluorescent proteins (FPs) and sensing domains into a single polypeptide. To address this, we developed FRET and lanthanide-based FRET (LRET) biosensors of Rac1 activation with two key features that enhance sensitivity and dynamic range. For one, alpha helical linker domains separate FRET partners and ensure a large conformational change and FRET increase when activated Rac1 at the biosensor C-terminus interacts with an amino-terminal Rac binding domain. Incorporation of a luminescent Tb(III) complex with long (~ ms) excited state lifetime as a LRET donor enabled time-gated luminescence measurements of Rac1 activity in cell lysates. The LRET dynamic range increased with ER/K linker length up to 1100% and enabled robust detection of Rac1 inhibition in 96-well plates. The ER/K linkers had a less pronounced, but still significant, effect on conventional FRET biosensors (with FP donors and acceptors), and we were able to dynamically image Rac1 activation at cell edges using fluorescence microscopy. The results herein highlight the potential of FRET and LRET biosensors with ER/K linkers for cell-based imaging and screening of protein activities.

Lanthanide-based resonance energy transfer biosensors for live-cell applications.

Lanthanide-based, Förster resonance energy transfer (LRET) biosensors enable sensitive, time-gated luminescence (TGL) imaging or multiwell plate analysis of protein-protein interactions (PPIs) in living mammalian cells. LRET biosensors are polypeptides that consist of an alpha-helical linker sequence sandwiched between a lanthanide complex-binding domain and a fluorescent protein (FP) with two interacting domains residing at each terminus. Interaction between the terminal affinity domains brings the lanthanide complex and FP in close proximity such that lanthanide-to-FP, LRET-sensitized emission is increased. A recent proof-of-concept study examined model biosensors that incorporated the affinity partners FKBP12 and the rapamycin-binding domain of m-Tor (FRB) as well as p53 (1-92) and HDM2 (1-128). The sensors contained an Escherichia coli dihydrofolate reductase (eDHFR) domain that binds with high selectivity and affinity to Tb(III) complexes coupled to the ligand trimethoprim (TMP). When cell lines that stably expressed the sensors were treated with TMP-Tb(III), TGL microscopy revealed dramatic differences (>500%) in donor- or acceptor-denominated, Tb(III)-to-GFP LRET ratios between open (unbound) and closed (bound) states of the biosensors. Much larger signal changes (>2500%) and Z'-factors of 0.5 or more were observed when cells were grown in 96-well or 384-well plates and analyzed using a TGL plate reader. In this chapter, we elaborate on the design and performance of LRET biosensors and provide detailed protocols to guide their use for live-cell microscopic imaging studies and high-throughput library screening.

Addressing depression and behavioral health needs through a digital program at scale.

Depression and anxiety disorders are prevalent mental health conditions; yet they are often unrecognized, under-addressed and/or under-treated, and specialty treatment for these conditions is oftentimes difficult to access. By acting either as a bridge to therapy or as a form of therapy, digital tools, such as those that provide internet-based cognitive behavioral therapy (iCBT), may help clinicians support their patients' mental health needs. At one academic health system, a digital mental health program was deployed in primary care and outpatient behavioral health programs to help patients meet needs identified through screening or clinical visits. Over the first two years of operation, 138 clinicians (40% of eligible clinicians) prescribed the program to 2,228 unique patients, from which 1,117 (48.9%) enrolled. Patients who enrolled tended to be younger and healthier than non-enrollees. On average, enrolled patients spent 114.6 minutes within the iCBT program. Clinical improvement was assessed using pre- and post PHQ-9 and GAD-7 scores for depression and anxiety, respectively. Pre/Post scores were compared using Wilcoxon Rank Sum test. Patients with at least moderate depression had an average 23% reduction in PHQ-9 scores (median change -3(interquartile range 7), p<0.001) and those with at least moderate anxiety had a 26% reduction in GAD-7 scores (-4(7), p<0.001). Improvements were clinically and statistically significant. Future steps include performing a cost analysis to understand whether models utilizing iCBT are net cost-saving for health systems.

Single-Chain Lanthanide Luminescence Biosensors for Cell-Based Imaging and Screening of Protein-Protein Interactions.

Lanthanide-based, Förster resonance energy transfer (LRET) biosensors enabled sensitive, time-gated luminescence (TGL) imaging or multiwell plate analysis of protein-protein interactions (PPIs) in living cells. We prepared stable cell lines that expressed polypeptides composed of an alpha helical linker flanked by a Tb(III) complex-binding domain, GFP, and two interacting domains at each terminus. The PPIs examined included those between FKBP12 and the rapamycin-binding domain of m-Tor (FRB) and between p53 (1-92) and HDM2 (1-128). TGL microscopy revealed dramatic differences (>500%) in donor- or acceptor-denominated, Tb(III)-to-GFP LRET ratios between open (unbound) and closed (bound) states of the biosensors. We observed much larger signal changes (>2,500%) and Z'-factors of 0.5 or more when we grew cells in 96- or 384-well plates and analyzed PPI changes using a TGL plate reader. The modular design and exceptional dynamic range of lanthanide-based LRET biosensors will facilitate versatile imaging and cell-based screening of PPIs.

Clinical Efficacy of Intra-articular Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Double-Blinded Prospective Randomized Controlled Clinical Trial.

BACKGROUND: Currently, there are limited nonoperative treatment options available for knee osteoarthritis (OA). Cell-based therapies have emerged as promising treatments for knee OA. Autologous stromal vascular fraction (SVF) has been identified as an efficient medium for intra-articular administration of progenitor cells and mesenchymal stem cells derived from adipose tissue. HYPOTHESIS: Patients receiving intra-articular SVF would show significantly greater improvement than patients receiving placebo injections, and this improvement would be dose dependent. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This was a multisite prospective double-blinded randomized placebo-controlled clinical trial. Adult patients with symptomatic knee OA were eligible. Thirty-nine patients were randomized to high-dose SVF, low-dose SVF, or placebo (1:1:1). SVF was obtained via liposuction, processed to create the cellular implant, and injected during the same clinical visit. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and magnetic resonance images were obtained preoperatively and at 6 and 12 months after injection. The Wilcoxon rank sum nonparametric test was utilized to assess statistical significance, and the Hodges-Lehmann location shift was used to assess superiority. RESULTS: The median percentage change in WOMAC score at 6 months after injection for the high-dose, low-dose, and placebo groups was 83.9%, 51.5%, and 25.0%, respectively. The high- and low-dose groups had statistically significant changes in WOMAC scores when compared with the placebo group (high dose, P = .04; low dose, P = .02). The improvements were dose dependent. The median percentage change in WOMAC score from baseline to 1 year after injection for the high-dose, low-dose, and placebo groups was 89.5%, 68.2%, and 0%, respectively. The high- and low-dose groups displayed a greater percentage change at 12 months when compared with the placebo group (high dose, P = .006; low dose, P = .009). Magnetic resonance image review revealed no changes in cartilage thickness after treatment. No serious adverse events were reported. CONCLUSION: Intra-articular SVF injections can significantly decrease knee OA symptoms and pain for at least 12 months. The efficacy and safety demonstrated in this placebo-controlled trial support its implementation as a treatment option for symptomatic knee OA. REGISTRATION: NCT02726945 (ClinicalTrials.gov identifier).

Preoperative Estimated Width of the Patellar Tendon for Anterior Cruciate Ligament Reconstruction.

This study aims to compare the actual patellar tendon width with the skin and magnetic resonance imaging (MRI) measurements and to describe a more accurate method to predict the actual patellar tendon width before anterior cruciate ligament reconstruction (ACLR).Thirty-nine patients undergoing primary ACLR were identified. Patients with patellar tendon width of less than 30 mm by skin or MRI measurements were excluded from the study. The actual patellar tendon width was measured as an intraoperative reading taken after surgical exposure. Mean difference between the skin and actual measurement and mean difference between the MRI and actual measurement was calculated. Paired t-test was run to determine any significant differences. A difference was also calculated between the actual measurement and the average sum of skin and MRI measurements for each patient. Skin thickness was compared to Δ (Δ = preincision skin measurement of patellar tendon width minus postincision actual measurement) by Spearman's correlation test. Mean difference between skin and actual measurements was 2.5 mm, with p = 0.001. Mean difference between MRI and actual measurement was -2.7 mm with p = 0.001. However, the mean difference between the actual and the average sum of skin and MRI measurements was 0.13 mm with p = 0.76. The Pearson's correlation coefficient, r s, between average sum of skin and MRI measurements and the actual measurement was 0.6 with p = 0.001. There was no correlation found between the skin thickness and Δ∙. This study indicates that there is a significant difference between the actual patellar tendon width and the measurement of the tendon taken using a ruler on the skin or using MRI image software. However, the average sum of skin and MRI measurements, which is not significantly different from the actual width, can accurately predict the actual patellar tendon width before ACLR. The study reflects level IV evidence.

Novel policing techniques decrease gun-violence and the cost to the healthcare system.

The objective was to investigate the effects of novel policing techniques on hospital-observed incidence, healthcare utilization, mortality and costs associated with gun violence, from the perspective of a level-1 trauma center. An eight-year retrospective review evaluating the clinical and financial effects of gunshot wound (GSW) encounters between January 1st, 2010 and December 31st, 2017. Individuals who presented to the emergency department (Level-1 trauma center in Camden, NJ) between January 1, 2010 and December 31, 2017 with GSW (995 encounters) were included; however, patients with incomplete financial or medical record data were excluded (55 encounters). Patients were subdivided into two cohorts: before and after changes in policing tactics (May 1st, 2013). 940 total firearm-related encounters were included in the study. Following the policing changes, the hospital-observed quarterly incidence of GSW encounters decreased by 22% post-policing changes, 44.3 to 34.6 (p = 0.038). Average quarterly days spent in-house for GSW treatment decreased 220.7 to 151.3 (31%) days. Hospital observed mortality increased from 13.5% of presentations to 17.3% of presentations (p = 0.106). Total cost savings associated with the policing change was roughly $254,000 per quarter (p = 0.023). In areas susceptible to high rates of gun violence, similar novel policing tactics could significantly decrease hospital-observed incidence, costs and healthcare utilization demanded by firearm-related injury.

The risk factors and an evidence-based protocol for the management of persistent wound drainage after total hip and knee arthroplasty.

BACKGROUND: Persistent wound drainage (PWD) is one of the major risk factors for periprosthetic joint infections (PJIs), arguably the most dreaded complication after total joint arthroplasty (TJA). The aim of this study was to identify the risk factors for PWD and provide a stepwise management protocol for it. METHODS: A retrospective review of 4873 TJAs was performed. After determining patients with PWD, a logistic regression model was designed to identify the risk factors using Charlson and Elixhauser comorbidity indexes. Finally, the protocol that was instituted for the management of PWD and its success rate was presented. RESULTS: The prevalence of PWD was 6.2% (302 of 4873). Of these, 196 did not require any surgical interventions, and drainage stopped with local wound care. 106 patients required surgical intervention, of which, 64 underwent superficial irrigation and debridement and 42 underwent deep irrigation and debridement with modular components exchange. Patients with PWD had significantly higher rates of PJI (odds ratio [OR]: 16.9; 95% confidence interval [CI]: 9.1-31.6). Risks factors were diabetes (OR: 21.2; 95% CI: 12.8-25.1), morbid obesity (OR: 17.3; 95% CI: 14.7-21.5), rheumatoid arthritis (OR: 14.2; 95% CI: 11.7-16.5), chronic alcohol use (OR: 4.3; 95% CI: 2.3-6.1), hypothyroidism (OR: 2.8; 95% CI: 1.3-4.2), and female gender (OR: 1.9; 95% CI: 1.1-2.2). CONCLUSIONS: Several modifiable risk factors of PWD were identified. Surgeons must be cognizant of these comorbidities and optimize patients' general health before an elective TJA. Our results demonstrated that PWD ceased in about 65% of the patients with local wound care measures alone. Patients with PWD were at substantially higher risk for PJI.

Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis.

Epithelial barrier loss is a driver of intestinal and systemic diseases. Myosin light chain kinase (MLCK) is a key effector of barrier dysfunction and a potential therapeutic target, but enzymatic inhibition has unacceptable toxicity. Here, we show that a unique domain within the MLCK splice variant MLCK1 directs perijunctional actomyosin ring (PAMR) recruitment. Using the domain structure and multiple screens, we identify a domain-binding small molecule (divertin) that blocks MLCK1 recruitment without inhibiting enzymatic function. Divertin blocks acute, tumor necrosis factor (TNF)-induced MLCK1 recruitment as well as downstream myosin light chain (MLC) phosphorylation, barrier loss, and diarrhea in vitro and in vivo. Divertin corrects barrier dysfunction and prevents disease development and progression in experimental inflammatory bowel disease. Beyond applications of divertin in gastrointestinal disease, this general approach to enzymatic inhibition by preventing access to specific subcellular sites provides a new paradigm for safely and precisely targeting individual properties of enzymes with multiple functions.

Clinical Biopsychosocial Reflection on Coping With Chronic Illness and Reliance Upon Nutrition Support: An Integrated Healthcare Approach.

Nutrition deficits are common in patients with chronic illnesses reliant upon nutrition support and can contribute to an increase in cognitive deficits that impact treatment adherence and challenge patients' abilities to cope and successfully implement appropriate psychological and psychosocial interventions. Adopting a multidisciplinary approach addresses biological, psychological, and social barriers that help patients, families, and caregivers develop and maintain proper nutrition behaviors that can enhance patients' quality of life and reduce frustration and misunderstandings with medical providers. This article is a review of the literature, and it advances the importance of encompassing a biopsychosocial approach when addressing the needs of individuals with nutrition support needs.

Matching into an Orthopedic Residency: Which Application Components Correlate with Final Rank List Order?

OBJECTIVE: To determine if any of the unique elements of the applications of medical students who were granted interviews to an orthopedic residency program correlate to the program's final rank order list of candidate residents. DESIGN: Eight domains of the standard residency application were considered as independent variables for 36 applicants. Personal, identifying information was removed from the application material within each domain, thus blinding the application domains for 5 core faculty members from the program to review and rank independently. These 8 domain rank lists were then compared to the program's final rank list order to determine the correlation of each domain with the final rank list order. SETTING: Academic medical center. PARTICIPANTS: Applicants to a university-based orthopedic surgery residency program who were granted interviews in the 2016 academic year. RESULTS: Two domains of the application correlated with the final rank list order: interview and personal statement. None of the other domains had a significant correlation with the final rank list order. Interobserver variability among the faculty members was high for the rankings of the different domains. CONCLUSIONS: Interview and personal statement were the only domains within the application that had correlation with the final rank list for an orthopedic residency program. A better understanding of how these 2 components affect the rank list may provide opportunity for process improvements.

Time-Gated Luminescence Detection of Enzymatically Produced Hydrogen Sulfide: Design, Synthesis, and Application of a Lanthanide-Based Probe.

Hydrogen sulfide (H2S) is now recognized as an important gaseous transmitter that is involved in a variety of biological processes. Here, we report the design and synthesis of a luminescent lanthanide biosensor for H2S, LP2-Cu(II)-Ln(III), a heterobinuclear metal complex that uses Cu(II) decomplexation to control millisecond-scale-lifetime-Tb(III)- or Eu(III)-emission intensity. LP2-Cu(II)-Ln(III) responded rapidly, selectively, and with high sensitivity to aqueous H2S. The probe's potential for biological applications was verified by measuring the H2S generated by the slow-releasing chemical-sulfide-donor GYY4147, by cystathionine γ-lyase (CSE), and by Na2S-stimulated HeLa cells.

Efficient route to pre-organized and linear polyaminopolycarboxylates: Cy-TTHA, Cy-DTPA and mono/di- reactive, tert-butyl protected TTHA/Cy-TTHA.

Pre-organized polyaminopolycarboxylate chelators Cy-TTHA and Cy-DTPA were synthesized via modular five-step syntheses from commercially available starting materials in ~ 62% and 47% overall yields, respectively. Furthermore, strategies are reported for the efficient preparation of mono- and di-reactive, tert-butyl-protected TTHA/Cy-TTHA to selectively functionalize central chelators' carboxylic acids.

Time Gated Luminescence Imaging of Immunolabeled Human Tissues.

Multiplexed immunofluorescence imaging of formalin-fixed, paraffin-embedded tissues is a powerful tool for investigating proteomic profiles and diagnosing disease. However, conventional immunofluorescence with organic dyes is limited in the number of colors that can be simultaneously visualized, is made less sensitive by tissue autofluorescence background, and is usually incompatible with commonly used hematoxylin and eosin staining. Herein, we demonstrate the comparative advantages of using time-gated luminescence microscopy in combination with an emissive Tb(III) complex, Lumi4-Tb, for tissue imaging in terms of sensitivity, multiplexing potential, and compatibility with common immunohistochemistry protocols. We show that time-gated detection of millisecond-scale Tb(III) emission increases signal-to-noise ratio relative to conventional steady-state detection of organic dye fluorescence and permits visualization of low-abundance tissue markers such as Bcl-6 or MSH-6. In addition, temporal separation of long- and short-lifetime (∼nanosecond) signals adds a second dimension for multiplexing and also permits detection of intermolecular Tb(III)-to-dye Förster resonance energy transfer. Furthermore, we demonstrate that the Lumi4-Tb complex is compatible with tyramide signal amplification and, unlike conventional organic dyes, can be reliably used on tissue stained with hematoxylin and eosin. Our results indicate that time-gated luminescence microscopy using Tb(III) labels can provide a sensitive and robust method to perform multiplexed immunofluorescence on archived or clinical tissue specimens.