Results of Randomized Controlled Trials of Platelet-Rich Plasma in Lower-Extremity Tendinopathy Are Not Influenced by Industry Sponsorship.

PURPOSE: To determine whether industry affiliation influences the results of randomized controlled trials (RCTs) studying the use of platelet-rich plasma (PRP) for the treatment of patellar or Achilles tendinopathy. METHODS: The PubMed, Scopus, Cochrane, and MEDLINE databases were searched in July 2023 for RCTs investigating PRP for the treatment of patellar or Achilles tendinopathy published between 2009 and July 2023. Industry affiliation was determined by analyzing each study's funding or conflict-of-interest section. Author disclosures were searched in the American Academy of Orthopaedic Surgeons disclosure database and the Centers for Medicare & Medicaid Services open payments database. An industry-affiliated (IA) designation was given if an author had a relevant disclosure or if the company that funded the study manufactured PRP. Otherwise, a non-industry-affiliated (NIA) designation was given. Fisher exact analysis was used to determine whether PRP had a favorable effect, no significant effect, or an unfavorable effect on outcome. RESULTS: Analysis was performed on 22 studies (10 IA and 12 NIA), with 17 studies (77.3%) reporting a conflict of interest or funding for the research, 4 (18.2%) reporting no conflict of interest, and 1 (4.5%) with no reporting. Of the 22 included studies, 8 (36.4%) reported favorable outcomes regarding PRP use and 14 (63.6%) reported no significant effect. Favorable outcomes were found in 4 of the 10 IA studies (40.0%), whereas no significant effect was reported in 6 (60.0%). The 12 NIA studies included 4 (33.3%) with favorable results and 8 (66.7%) with no significant effect. The comparison between industry affiliation and results reported was not statistically significant (P > .999). CONCLUSIONS: The results of RCTs evaluating the use of PRP in lower-extremity tendinopathy were not influenced by industry sponsorship. CLINICAL RELEVANCE: Most biomedical research is funded through industry sponsorship. Although this relation is necessary as technologies are developed, it is important to scrutinize studies for evidence of industry bias to understand how this bias may be affecting study results published in the literature.

Reporting Bias in the Form of Positive Spin Is Highly Prevalent in Abstracts of Systematic Reviews on Primary Repair of the Anterior Cruciate Ligament.

PURPOSE: To analyze reporting bias in the form of spin present in systematic reviews and meta-analyses on the topic of primary anterior cruciate ligament (ACL) repair. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed throughout this study. Peer-reviewed systematic reviews were collected from 3 databases (PubMed, Scopus, and SPORTDiscus), and their abstracts were assessed for the 15 most common types of spin. Articles were excluded if they were not published in English, had no evidence, were retracted, were published without an abstract, did not have full text available, or included cadaveric or nonhuman subjects. Full text quality was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews Version 2). Fisher exact tests were used to examine associations between the different types of spin and other study characteristics such as AMSTAR 2 confidence rating, study design, and level of evidence. RESULTS: Spin was present in the abstracts of 13 of 15 articles (86.7%). There were significant associations between PRISMA adherence and lower incidences of spin types 3, 6, and 8 (P = .029 for each). A critically low AMSTAR 2 confidence rating was significantly associated with an increased incidence of spin type 9 (P = .01), and a higher AMSTAR 2 score was significantly associated with decreased spin type 4 and type 5 (P = .039 and P = .048, respectively). A more recent year of publication was correlated with a lower incidence of spin type 14 (P = .044). CONCLUSIONS: Spin is present in most systematic reviews and meta-analyses regarding primary repair of the ACL, with two-thirds of abstracts spinning evidence in favor of ACL repair. Standardized guidelines including the PRISMA guidelines and the AMSTAR 2 assessment tool were negatively correlated with spin. More recently published articles were found to contain significantly less spin, as were articles published in journals with higher Clarivate Impact Factors and Scopus CiteScores. LEVEL OF EVIDENCE: Level V, systematic review of Level III through V studies.

Studies With Direct Industry Affiliation Are More Likely to Report Positive Results in Randomized Controlled Trials for Platelet-Rich Plasma Use in Rotator Cuff Tears: A Systematic Review.

PURPOSE: To perform a systematic review to evaluate the effect of industry affiliation on the outcomes of randomized controlled trials for platelet-rich plasma (PRP) injections in rotator cuff tears METHODS: The PubMed, SPORTDiscus, and Scopus databases were searched from 2010 to the present for the terms "rotator cuff" and "platelet-rich plasma." The inclusion criteria were randomized controlled trials comparing PRP with controls for the treatment of rotator cuff tears, and the exclusion criteria were systematic reviews, meta-analyses, case reports, cohort studies, basic science studies, studies of Level III or below, and studies not in English. Degree of industry affiliation was categorized into 3 groups: directly, indirectly, and not affiliated. Direct affiliation required the study or its authors to receive financial support from the company manufacturing the devices used in the study to prepare or administer PRP. Indirect affiliation required financial association with a different company that produces or administers PRP than the company in the study. Studies were classified as favorable if study outcomes achieved significance (P < .05) of PRP over controls or as analogous if there was no statistical significance between PRP and controls. Data were analyzed using the χ2 test and Fisher exact test. RESULTS: Of the 47 studies selected for analysis, 8 (17.0%) had no direct industry affiliation; 9 (19.1%) had indirect affiliation; and 30 (63.8%) had no industry affiliation. Of the studies, 22 (46.8%) reported favorable results with PRP compared with controls and 25 (53.2%) showed analogous results between PRP and controls. Degree of industry affiliation was significantly associated with an increased likelihood of reporting favorable study outcomes (P = .041). Directly affiliated studies had a significantly increased likelihood of reporting favorable results (P = .024) compared with indirectly affiliated studies. CONCLUSIONS: Studies that used PRP produced by companies that directly funded the studies or were financially affiliated with the authors were significantly more likely to report favorable results. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

ChatGPT, Bard, and Bing Chat are large language processing models that answered OITE questions with a similar accuracy to first-year orthopaedic surgery residents.

PURPOSE: To assess ChatGPT, Bard, and BingChat's ability to generate accurate orthopaedic diagnosis or corresponding treatments by comparing their performance on the Orthopaedic In-Training Examination (OITE) to orthopaedic trainees. METHODS: OITE question sets from 2021 and 2022 were compiled to form a large set of 420 questions. ChatGPT (GPT3.5), Bard, and BingChat were instructed to select one of the provided responses to each question. The accuracy of composite questions was recorded and comparatively analyzed to human cohorts including medical students and orthopaedic residents, stratified by post-graduate year. RESULTS: ChatGPT correctly answered 46.3% of composite questions whereas BingChat correctly answered 52.4% and Bard correctly answered 51.4% of questions on the OITE. Upon excluding image-associated questions, ChatGPT, BingChat, and Bard's overall accuracies improved to 49.1%, 53.5%, and 56.8%, respectively. Medical students and orthopaedic residents (PGY1-5) correctly answered 30.8%, 53.1%, 60.4%, 66.6%, 70.0%, and 71.9%, respectively. CONCLUSION: ChatGPT, Bard, and BingChat are AI models that answered OITE questions with an accuracy similar to that of first-year orthopaedic surgery residents. ChatGPT, Bard, and BingChat achieved this result without using images or other supplementary media that human test takers are provided.

Most Major Hospitals Fail to Comply With Federal Price Transparency Regulations.

PURPOSE: To present hospital compliance with federal price transparency regulations for sports medicine procedures. METHODS: Online price estimator and machine-readable files were recovered for U.S. News and World Report's top 100 orthopaedic hospitals. From June to November 2023, compliance and monetary values were recorded for each of Centers for Medicare and Medicaid Services price transparency regulations. Price estimator data were assessed on the basis of hospital placement in the bottom and top 50 of the 100 institutions under review, as well as by region (Northeast, South, Midwest, West). Statistical analyses included 2-sample t tests and Kruskal-Wallis tests. RESULTS: In total, 95% of hospitals had a price estimator tool for both subacromial decompression (Current Procedural Terminology [CPT] code 29826) and meniscectomy (CPT code 29881). Only 38% were compliant with all regulations for subacromial decompression and 39% for meniscectomy; the remaining did not list minimum or maximum procedure charges. Higher-ranked hospitals were significantly more likely to charge a greater cash price for subacromial decompression and meniscectomy (P = .040 and P = .009, respectively). Compliance with machine-readable file reporting was poor, with less than 20% meeting requirements for each CPT code. Reported prices varied greatly by hospital. CONCLUSIONS: This study demonstrates that U.S. News and World Report's top 100 orthopaedic hospitals exhibit poor overall compliance with federal price transparency regulations for sports medicine procedures. Most often they lack full compliance by not reporting minimum or maximum charges as part of their price estimator tool or do not report procedure prices in their machine-readable files. Hospitals also exhibit wide variation in prices reported for specific procedures. CLINICAL RELEVANCE: Consumer price transparency continues to be an important goal in health care, as it allows patients to make informed decisions when selecting appropriate treatment options and providers. To realize the full benefits of price transparency, hospitals should address areas of improvement.

Randomized controlled trials in the shoulder arthroplasty literature rarely include key demographic and socioeconomic patient data.

BACKGROUND: It is well known that socioeconomic and demographic variables can greatly affect health outcomes. Previous studies across medical and surgical subspecialties have demonstrated that these variables are frequently under-reported in randomized controlled trials (RCTs). No such study currently exists that examines rates of reporting of sociodemographic variables in shoulder arthroplasty RCTs. This study aims to present these rates and explore the impact of failing to report socioeconomic variables in shoulder arthroplasty RCTs. METHODS: The PubMed database was queried for the term shoulder arthroplasty. Sixty-five RCTs from the past 10 years were identified for inclusion from 5 high-impact orthopedic surgery journals. Each RCT was analyzed for patient age and sex or gender as well as the following sociodemographic variables: race, ethnicity, insurance status, income, work status, and education. It was also noted whether each of the above variable was mentioned in the results section of the article. Data were presented in a descriptive fashion as well as analyzed using χ2 and Fisher exact tests where appropriate. RESULTS: From 2014 to 2023, the 65 shoulder arthroplasty RCTs published reported age in 40 of 65 (61.5%) in their results sections and 61 of 65 (93.8%) in any section. Sex or gender was reported in 27 of 65 (41.5%) in their results sections and 61 of 65 (93.8%) in any section. No articles included any sociodemographic variables in the results section. Reporting rates for sociodemographic variables in any section were as follows: race, 6 of 65 (9.2%); ethnicity, 5 of 65 (7.7%); work status, 4 of 65 (6.2%); and insurance status, 1 of 65 (1.5%). No studies included income or education of the enrolled patients. There was no difference in reporting sociodemographic variables by journal (P = .45) or by year of publication (P = .57). However, no study prior to 2020 included any sociodemographic variable (0 of 27, 0%), whereas from 2020 onward 6 studies included at least 1 (6 of 38, 15.8%). Sociodemographic variables were reported significantly less frequently than age and sex or gender (P = .001). DISCUSSION: Our study found sociodemographic variables are rarely reported in shoulder arthroplasty RCTs, whereas age and sex or gender are reported with great frequency. In order to understand the results of shoulder arthroplasty RCTs, apply their findings to the care of our patients, and address health disparities, we must ensure these studies include patient sociodemographic data.

Shoulder arthroplasty for inflammatory arthritis is associated with higher rates of medical and surgical complications: a nationwide matched cohort analysis from 2016-2020.

BACKGROUND: Inflammatory arthritis (IA) represents a less common indication for anatomic and reverse total shoulder arthroplasty (TSA) than osteoarthritis (OA). The safety and efficacy of anatomic and reverse TSA in this population has not been as well studied compared to OA. We analyzed the differences in outcomes between IA and OA patients undergoing TSA. METHODS: Patients who underwent primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) from 2016-2020 were identified in the Premier Healthcare Database. Inflammatory arthritis (IA) patients were identified using International Classification of Diseases, Tenth Revision, diagnosis codes and compared to osteoarthritis controls. Patients were matched in a 1:8 fashion by age (±3 years), sex, race, and presence of pertinent comorbidities. Patient demographics, hospital factors, and patient comorbidities were compared. Multivariate regression was performed following matching to account for any residual confounding and 90-day complications were compared between the 2 cohorts. Descriptive statistics and regression analysis were employed with significance set at P < .05. RESULTS: Prior to matching, 5685 IA cases and 93,539 OA controls were identified. Patients with IA were more likely to be female, have prolonged length of stay and increased total costs (P < .0001). After matching and multivariate analysis, 4082 IA cases and 32,656 controls remained. IA patients were at increased risk of deep wound infection (OR 3.14, 95% CI 1.38-7.16, P = .006), implant loosening (OR 4.11, 95% CI 1.17-14.40, P = .027), and mechanical complications (OR 6.34, 95% CI 1.05-38.20, P = .044), as well as a decreased risk of postoperative stiffness (OR 0.36, 95% CI 0.16-0.83, P = .002). Medically, IA patients were at increased risk of PE (OR 2.97, 95% CI 1.52-5.77, P = .001) and acute blood loss anemia (OR 1.27, 95% CI 1.12-1.44, P < .0001). DISCUSSION AND CONCLUSION: Inflammatory arthritis represents a distinctly morbid risk profile compared to osteoarthritis patients with multiple increased surgical and postoperative medical complications in patients undergoing aTSA and rTSA. Surgeons should consider these potential complications and employ a multidisciplinary approach in preoperative risk stratification of IA undergoing shoulder replacement.

Perioperative intravenous dexamethasone use is not associated with periprosthetic joint infection or wound healing complications following shoulder arthroplasty.

BACKGROUND: Perioperative intravenous (IV) dexamethasone is commonly used in lower extremity total joint arthroplasty to manage postoperative pain and nausea/vomiting, and recent studies have demonstrated that its use may lower rates of acute postoperative medical complications. However, there is limited information regarding the safety and efficacy of IV dexamethasone in patients undergoing total shoulder arthroplasty (TSA). Additionally, there is concern surrounding corticosteroid use prior to surgery as preoperative corticosteroid injections have been associated with adverse outcomes after TSA, including periprosthetic joint infection (PJI) and revision surgery. Thus, the purpose of this study was to evaluate the effect of perioperative IV dexamethasone on 90-day rates of PJI, wound complications, and medical complications after TSA. METHODS: The Premiere national hospital database was used to identify adult patients undergoing elective TSA between 2016 and 2020; patients were excluded if they were under 18 years old, were undergoing revision TSA, or had a prior proximal humerus open reduction internal fixation procedure. Patients who did and did not receive perioperative IV dexamethasone were then compared in both univariate and multivariate analyses. A Bonferroni correction was utilized to adjust for multiple comparisons. The primary end point was risk of acute infectious complications within 90 days of surgery, including PJI and wound infection/dehiscence. Secondary end points included acute pulmonary, renal, and thromboembolic complications. RESULTS: A total of 135,333 patients underwent TSA during the study period; 61.2% underwent reverse total shoulder arthroplasty, 33.8% underwent anatomic total shoulder arthroplasty, and 5.0% underwent hemiarthroplasty. From 2016 to 2020, perioperative IV dexamethasone use increased by 135%. Multivariate analysis revealed that patients who received perioperative IV dexamethasone did not have increased odds of PJI, superficial wound infection, or wound dehiscence (P = .15-.47) but did have decreased odds of sepsis (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.55-0.81) and other medical complications such as urinary tract infection and acute kidney injury. Additionally, there was a trend towards decreased 90-day hospital readmission (OR 0.88, 95% CI 0.81-0.96, P = .003). CONCLUSIONS: Perioperative IV dexamethasone was not associated with increased risk of acute infectious and wound healing complications. Moreover, patients who received perioperative IV dexamethasone had decreased odds of medical complications and trended toward lower rates of 90-day hospital readmission. The results of this study support the safety of perioperative IV dexamethasone use in patients undergoing elective TSA.

Harms reporting in randomized controlled trials underpinning the American Academy of Orthopaedic Surgeons clinical practice guidelines for glenohumeral osteoarthritis.

BACKGROUND: Glenohumeral osteoarthritis is one of the most common causes of shoulder pain. As such, the American Academy of Orthopaedic Surgeons (AAOS) has developed clinical practice guidelines (CPGs) to address the management of glenohumeral osteoarthritis. These CPG recommendations stem from the findings of randomized controlled trials (RCTs), which have been shown to influence clinical decision making and health policy. Therefore, it is essential that trial outcomes, including harms data (ie, adverse events), are adequately reported. We intend to evaluate the reporting quality of harms-related data in orthopedic literature specifically relating to AAOS CPG recommendations on the management of glenohumeral osteoarthritis. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews (PRISMA) as well as guidance for reporting meta-research. The AAOS CPGs for glenohumeral osteoarthritis were obtained from orthoguidelines.org, and 2 authors independently screened the guidelines for the RCTs referenced. A total of 14 studies were identified. Data were extracted from the 14 included studies independently by the same 2 authors. Adherence to the Consolidated Standards of Reporting Trials (CONSORT) Extension for Harms Checklist was assessed using an 18-item scoring chart, with 1 point being awarded for meeting a checklist item and 0 points being awarded for not meeting a checklist item. Descriptive statistics, such as frequencies, percentages, and 95% confidence intervals were used to summarize RCT adherence to the CONSORT checklist. RESULTS: The average score among the studies included was 7.36/18 items (39% adherence). No study adhered to all criteria, with the highest-performing study meeting 11 of 18 items (58%) and the lowest meeting 3 of 18 items (16%). A positive correlation between checklist score and year of publication was observed, with studies published more recently receiving a higher score on the CONSORT checklist (P < .05). Studies that disclosed funding information received a higher score than those that did not (P < .05), but there was no significant difference when the different funding sources were compared. Finally, double-blinded studies scored higher on the checklist than those with lower levels of blinding (single or no blinding, P < .05). CONCLUSION: Adverse events are poorly reported amongst RCTs cited as supporting evidence for AAOS Management of Glenohumeral Osteoarthritis CPGs, evidenced by a CONSORT checklist compliance rate of only 41% in this study. We recommend the development of an updated checklist with information that makes it easier for authors to recognize, evaluate, and report on harms data. Additionally, we encourage authors to include information about adverse events or negative outcomes in the abstract.

Evaluation of spin in systematic reviews on the use of tendon transfer for massive irreparable rotator cuff tears.

PURPOSE: To identify, describe and account for the incidence of spin in systematic reviews and meta-analyses of tendon transfer for the treatment of massive, irreparable rotator cuff tears. The secondary objective was to characterize the studies in which spin was identified and to determine whether identifiable patterns exist among studies with spin. METHODS: This study was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each abstract was assessed for the presence of the 15 most common types of spin derived from a previously established methodology. General data that were extracted included study title, authors, publication year, journal, level of evidence, study design, funding source, reported adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, preregistration of the study protocol, and methodologic quality per A Measurement Tool to Assess Systematic Reviews Version 2 (AMSTAR 2). RESULTS: The search yielded 53 articles, of which 13 were included in the final analysis. Articles were excluded if they were not published in a peer reviewed journal, not written in English, utilized cadaveric or nonhuman models, or lacked an abstract with accessible full text. 53.8% (7/13) of the included studies contained at least 1 type of spin in the abstract. Type 5 spin ("The conclusion claims beneficial effect of the experimental treatment despite a high risk of bias in primary studies") was the most common, appearing in 23.1% (3/13) of included abstracts. Nine of the spin categories did not appear in any of the included abstracts. A lower AMSTAR 2 score was significantly associated with the presence of spin in the abstract (P < .006). CONCLUSION: Spin is highly prevalent in the abstracts of systematic reviews and meta-analyses concerning tendon transfer for massive rotator cuff tears. A lower overall AMSTAR 2 rating was associated with a higher incidence of spin. Future studies should continue to explore the prevalence of spin in orthopedic literature and identify any factors that may contribute to its presence.

Effect of body mass index on complications following total shoulder arthroplasty: a population-wide analysis.

BACKGROUND: Evidence regarding the effect of body mass index (BMI) on complications following anatomic shoulder arthroplasty (aTSA) and reverse shoulder arthroplasty (rTSA) remains controversial. This high-powered study examines the effect of BMI on surgical and medical complications following aTSA and rTSA. METHODS: This retrospective cohort study was conducted using the Premier Healthcare Database to query all adult patients who underwent primary, elective TSA (aTSA, rTSA) from 2016 to 2020. Patients eligible for inclusion were identified using International Classification of Diseases -10 and CPT codes for primary TSA. Patients were stratified into 3 subgroups based on BMI (BMI <30 kg/m2, BMI 30-35 kg/m2, BMI >35 kg/m2). The primary endpoints assessed were 90-day risks of postoperative complications, revisions, and readmissions among the 3 BMI groups undergoing primary TSA. RESULTS: A total of 32,645 patients were analyzed; 10,951 patients underwent aTSA and 21,694 patients underwent rTSA. Patient populations for aTSA and rTSA differed significantly across all BMI categories in terms of age, sex, cost of care, and insurance status. After multivariate regression analysis, there was no increased risk of surgical complications in the aTSA and rTSA cohorts with BMI 30-35 kg/m2 and BMI >35 kg/m2. In the aTSA cohort, rates of acute respiratory failure (adjusted Odds Ratio [aOR] 2.65) was all significantly higher in the BMI >35 kg/m2 group. As for rTSA cohort, acute respiratory failure (aOR 1.67) and acute renal failure (aOR 1.53) were significantly higher in the BMI >35 kg/m2 group. CONCLUSION: While we found no increased risk of immediate postoperative surgical risks, patients with a BMI >35 kg/m2 demonstrated greater risk of medical complications after rTSA. Given this trend, providers should exercise caution in patient selection for TSA and counsel obese patients as to these increased risks. Future studies should aim to provide a more comprehensive picture of the effect of BMI on functional outcomes after TSA.

Evaluation of spin in reviews of biodegradable balloon spacers for massive irreparable rotator cuff tears.

HYPOTHESIS: Clinical studies are often at risk of spin, a form of bias where beneficial claims are overstated while negative findings are minimized or dismissed. Spin is often more problematic in abstracts given their brevity and can result in the misrepresentation of a study's actual findings. The goal of this study is to aggregate primary and secondary studies reporting the clinical outcomes of the use of subacromial balloon spacers in the treatment of massive irreparable rotator cuff tears to identify the incidence of spin and find any significant association with study design parameters. MATERIALS AND METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Independent searches were completed on 2 databases (PubMed and Embase) for primary studies, systematic and current concepts reviews, and meta-analyses and the results were compiled. Two authors independently screened the studies using a predetermined inclusion criteria and aggregated data including titles, publication journals and years, authors, study design, etc. Each study was independently assessed for the presence of 15 different types of spin. Statistical analysis was conducted to identify associations between study characteristics and spin. RESULTS: Twenty-nine studies met the inclusion criteria for our analysis, of which 10 were reviews or meta-analyses and 19 were primary studies. Spin was identified in every study except for 2 (27/29, 93.1%). Type 3 spin, "Selective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention" and type 9 spin, "Conclusion claims the beneficial effect of the experimental treatment despite reporting bias" were most frequently noted in our study, both observed in 12/29 studies (41.4%). Date of publication, and adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses or "The International Prospective Register of Systematic Reviews" were study characteristics associated with a higher rate of certain types of spin. There was a statistically significant association between disclosure of external study funding source and the presence of spin type 4, but none of the other forms of spin. CONCLUSION: Spin is highly prevalent in the abstracts of primary studies, systematic reviews, and meta-analyses discussing the use of subacromial balloon spacer technology in the treatment of massive irreparable rotator cuff tears. Our findings revealed that spin in the abstract tended to favor the balloon spacer intervention. Further efforts are required in the future to mitigate spin within the abstracts of published manuscripts.

Role of PLGA Variability in Controlled Drug Release from Dexamethasone Intravitreal Implants.

Long-acting injectable formulations based on poly(lactide-co-glycolide) (PLGA) have been commercialized for over 30 years in at least 20 FDA-approved products. These formulations offer several advantages, including reduced dosing frequency, improved patient compliance, and maintenance of therapeutic levels of drug. Despite extensive studies, the inherent complexity of the PLGA copolymer still poses significant challenges associated with the development of generic formulations having drug release profiles equivalent to those of the reference listed drugs. In addition, small changes to PLGA physicochemical properties or the drug product manufacturing process can have a major impact on the drug release profile of these long-acting formulations. This work seeks to better understand how variability in the physicochemical properties of similar PLGAs affects drug release from PLGA solid implants using Ozurdex (dexamethasone intravitreal implant) as the model system. Four 50:50, acid-terminated PLGAs of similar molecular weights were used to prepare four dexamethasone intravitreal implants structurally equivalent to Ozurdex. The PLGAs were extensively characterized by using a variety of analytical techniques prior to implant manufacture using a continuous, hot-melt extrusion process. In vitro release testing of the four structurally equivalent implants was performed in both normal saline and phosphate-buffered saline (PBS), yielding drastically different results between the two methods. In normal saline, no differences in the release profiles were observed. In PBS, the drug release profiles were sensitive to small changes in the residual monomer content, carboxylic acid end group content, and blockiness of the polymers. This finding further underscores the need for a physiologically relevant in vitro release testing method as part of a robust quality control strategy for PLGA-based solid implant formulations.

Harms Reporting in Randomized Controlled Trials Underpinning the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines for Distal Radius Fractures.

PURPOSE: The purpose of this study was to measure the harms-related reporting among randomized controlled trials (RCTs) cited as supporting evidence for the American Academy of Orthopaedic Surgeons clinical practice guidelines regarding the management of distal radius fractures. METHODS: We adhered to the guidance for reporting metaresearch and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines throughout the course of this investigation. We used the American Academy of Orthopaedic Surgeons clinical practice guidelines for distal radius fractures available on Orthoguidelines.org. A linear regression analysis was conducted to model the relationship between the year of publication and the total Consolidated Standards of Reporting Trials percentage adherence over time. RESULTS: Thirty-five RCTs were included in the final sample. The average number of Consolidated Standards of Reporting Trials Extension for Harms items adequately reported across all included RCTs was 9.2 (9.2/18, 50.9%). None of the included trials adequately reported all 18 items. Ten items had a compliance of more than 50% (10/18, 55.6%), 4 items had a compliance of 20%-50% (4/18, 22.2%), and 4 items had a compliance of less than 20% (4/18, 22.2%). The results of the linear regression model showed no significant improvement in Consolidated Standards of Reporting Trials Harms reporting over time. CONCLUSIONS: Adverse events are incompletely reported among RCTs cited as supporting evidence for American Academy of Orthopaedic Surgeons clinical practice guidelines for the management of distal radius fractures. CLINICAL RELEVANCE: Given our findings, specific attention should be paid to improving the standardization of the classification of adverse events to facilitate ease in the reporting process.

Return to Sport Following Distal Triceps Repair.

PURPOSE: The purpose of this investigation was to examine the timeline of return-to-sport following distal triceps repair; evaluate the degree of participation and function upon returning to sport; and identify risk factors for failure to return to sport. METHODS: Patients who underwent distal triceps repair with a minimum of 1 year of follow-up were retrospectively reviewed. Patients completed a subjective sports questionnaire and were scored on a visual analog scale for pain; the Mayo Elbow Performance Index; the Quick Disabilities of the Arm, Shoulder, and Hand; and the Single Assessment Numerical Evaluation. RESULTS: Out of 113 eligible patients who had a distal triceps repair, 81 patients (71.7%) were contacted. Sixty-eight patients (84.0%) who participated in sports prior to surgery were included at 6.0 ± 4.0 years after surgery, and the average age was 46.6 ± 11.5 years. Sixty-one patients (89.7%) resumed playing at least 1 sport by 5.9 ± 4.4 months following distal triceps repair. However, 18 patients (29.5%) returned to a lower level of activity intensity. The average postoperative Quick Disabilities of the Arm, Shoulder, and Hand; Mayo Elbow Performance; visual analog scale for pain; and Single Assessment Numerical Evaluation scores were 8.2 ± 14.0, 89.5 ± 13.4, 2.0 ± 1.7, and 82.2 ± 24.3, respectively. No patients underwent revision surgery at the time of final follow-up. CONCLUSIONS: Distal triceps repair enables 89.7% of patients to return to sport by 5.9 ± 4.4 months following surgery. However, 29.5% of patients were unable to return to their preinjury level of activity. It is imperative that patients are appropriately educated to manage postoperative expectations regarding sport participation following distal triceps repair. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

High Rate of Return to Work by 3 Months Following Latarjet for Anterior Shoulder Instability.

PURPOSE: To evaluate the rate and duration of return to work in patients undergoing Latarjet for failed soft-tissue stabilization or glenoid bone loss. METHODS: Consecutive patients undergoing Latarjet from 2005 to 2015 at our institution were retrospectively reviewed at a minimum of 2 years postoperatively. Patients completed a standardized and validated work questionnaire, Western Ontario Shoulder Instability Index Survey, and a satisfaction survey. RESULTS: Of 89 eligible patients who had Latarjet, 67 patients (75.3%) responded to the questionnaire, of whom 51 patients (76.1%) were employed within 3 years before surgery (mean age: 29.9 ± 11.8 years; mean follow-up: 54.6 ± 11.9 months) and had an average glenoid bone loss of 14.5 ± 6.1%. Fifty patients (98.0%) returned to work by 2.7 ± 3.0 months postoperatively; 45 patients (88.2%) patients returned to the same level of occupational intensity. Those who held sedentary, light, moderate, or heavy intensity occupations returned to their previous occupation at a rate of 100.0%, 93.3%, 90.0%, and 66.7% (P = .2) at a duration of 1.2 ± 1.6 months, 1.8 ± 1.9 months, 3.1 ± 3.5 months, and 6.5 ± 4.1 months (P = .001), respectively. The average postoperative Western Ontario Shoulder Instability Index score was 70.9 ± 34.2. Fifty patients (98.0%) noted at least "a little improvement" in their quality of life following surgery, with 35 patients (68.6%) noting great improvement. Furthermore, 49 patients (96.1%) reported being satisfied with their procedure, with 25 patients (49.0%) reporting being very satisfied. Four patients (7.8%) returned to the operating room, with 1 patient (2.0%) requiring arthroscopic shoulder stabilization. CONCLUSIONS: Approximately 98% of patients who underwent Latarjet returned to work by 2.7 ± 3.0 months postoperatively. Patients with greater-intensity occupations had a longer duration of absence before returning to their preoperative level of occupational intensity. Information regarding return to work is imperative in preoperative patient consultation to manage expectations. LEVEL OF EVIDENCE: IV, case series.

Patient-reported outcome scores following patellar instability surgery-high prevalence does not equal high responsiveness: a systematic review.

PURPOSE: The purpose of this study was to determine the utilization and responsiveness of common patient-reported outcomes (PROs) in patients undergoing surgery for patellar instability. METHODS: Using PRISMA guidelines, a systematic review of studies reporting outcomes following surgical intervention for patellar instability was conducted using Pubmed, Cochrane, OVID Medline, and Google Scholar. Subgroup analysis of articles reporting at least two PROs with baseline and follow-up data were used to evaluate responsiveness of instruments using relative efficiency and effect size. RESULTS: From the search, 2,848 unique articles were found, of which 178 were included in final analysis (7,122 patients, mean age 22.6, 63.6% female). The most commonly used PRO was the Kujala score (79.2%), followed by the Lysholm (34.8%), and Tegner (30.9%). Seventy-nine articles were eligible for subgroup analysis. The Kujala had a higher relative efficiency than ten of the 14 instruments to which it was compared but had lower relative efficiency compared to the IKDC and Lysholm scores. The Banff Patella Instability Instrument (BPII) and the Norwich score, condition-specific tools, were unable to be fully assessed due to rarity of use and lack of comparisons. CONCLUSION: The hypothesis that the Kujala score is the most commonly used PRO for patellar instability, although other instruments offer greater efficiency was supported by our results. The IKDC and Lysholm scores had similar effect sizes but higher relative efficiencies than the Kujala, thus suggesting better responsiveness. This analysis adds useful information for surgeons on the effectiveness of the most common PRO's for evaluating patellofemoral instability outcomes. LEVEL OF EVIDENCE: Level III.

Prediction of total healthcare cost following total shoulder arthroplasty utilizing machine learning.

BACKGROUND: Given the increase in demand in treatment of glenohumeral arthritis with anatomic total (aTSA) and reverse shoulder arthroplasty (RTSA), it is imperative to improve quality of patient care while controlling costs as private and federal insurers continue its gradual transition toward bundled payment models. Big data analytics with machine learning shows promise in predicting health care costs. This is significant as cost prediction may help control cost by enabling health care systems to appropriately allocate resources that help mitigate the cause of increased cost. METHODS: The Nationwide Readmissions Database (NRD) was accessed in 2018. The database was queried for all primary aTSA and RTSA by International Classification of Diseases, Tenth Revision (ICD-10) procedure codes: 0RRJ0JZ and 0RRK0JZ for aTSA and 0RRK00Z and 0RRJ00Z for RTSA. Procedures were categorized by diagnoses: osteoarthritis (OA), rheumatoid arthritis (RA), avascular necrosis (AVN), fracture, and rotator cuff arthropathy (RCA). Costs were calculated by utilizing the total hospital charge and each hospital's cost-to-charge ratio. Hospital characteristics were included, such as volume of procedures performed by the respective hospital for the calendar year and wage index, which represents the relative average hospital wage for the respective geographic area. Unplanned readmissions within 90 days were calculated using unique patient identifiers, and cost of readmissions was added to the total admission cost to represent the short-term perioperative health care cost. Machine learning algorithms were used to predict patients with immediate postoperative admission costs greater than 1 standard deviation from the mean, and readmissions. RESULTS: A total of 49,354 patients were isolated for analysis, with an average patient age of 69.9 ± 9.6 years. The average perioperative cost of care was $18,843 ± $10,165. In total, there were 4279 all-cause readmissions, resulting in an average cost of $13,871.00 ± $14,301.06 per readmission. Wage index, hospital volume, patient age, readmissions, and diagnosis-related group severity were the factors most correlated with the total cost of care. The logistic regression and random forest algorithms were equivalent in predicting the total cost of care (area under the receiver operating characteristic curve = 0.83). CONCLUSION: After shoulder arthroplasty, there is significant variability in cumulative hospital costs, and this is largely affected by readmissions. Hospital characteristics, such as geographic area and volume, are key determinants of overall health care cost. When accounting for this, machine learning algorithms may predict cases with high likelihood of increased resource utilization and/or readmission.

Evaluation of spin in systematic reviews and meta-analyses of superior capsular reconstruction.

BACKGROUND: Small, preliminary studies and the systematic reviews on superior capsular reconstruction (SCR) that collate data are at increased risk spin. This study's primary objective was to identify, describe, and account for the incidence of spin in systematic reviews of SCR. This study's secondary objective was to characterize the studies in which spin was identified to determine whether identifiable patterns of characteristics exist among studies with spin. METHODS: This study was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a predetermined protocol. A search was conducted on the PubMed and Embase databases for systematic reviews and meta-analyses on SCR. Screening and data extraction were conducted independently by 2 authors. Each included study's abstract was assessed for the presence of the 15 most common types of spin, with full texts reviewed during cases of disagreement or for clarification. General data that were extracted included study title, authors, publication year, journal, level of evidence, study design, funding source, reported adherence to PRISMA guidelines, preregistration of the study protocol, and primary and secondary outcome measures. Full texts were used in the assessment of study quality per AMSTAR 2. RESULTS: We identified 53 studies during our search, of which 17 met the inclusion criteria. At least 1 form of spin was observed in all 17 studies. The most common types of spin were type 5 ("The conclusion claims the beneficial effect of the experimental treatment despite a high risk of bias in primary studies") and type 9 ("Conclusion claims the beneficial effect of the experimental treatment despite reporting bias"), both of which were observed in 11 studies (11 of 17, 65%). A statistically significant association between lower level of evidence and type 5 ("The conclusion claims the beneficial effect of the experimental treatment despite a high risk of bias in primary studies") was observed (P = .0175). A statistically significant association was also found between more recent year of publication and the spin category misleading interpretation (P = .0398), and between lower AMSTAR 2 score and type 13 ("Failure to specify the direction of the effect when it favors the control intervention") (P = .0260). No other statistical associations between other study characteristics were observed. CONCLUSION: Spin is highly prevalent in abstracts of SCR systematic reviews and meta-analyses. An association was found between the presence of spin and lower level of evidence, year of publication, and AMSTAR 2 ratings.

Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy.

In the present work, we investigated the role of natural killer (NK) cells in combination therapy with oncolytic virus (OV) and bortezomib, a proteasome inhibitor. NK cells display rapid and potent immunity to metastatic and hematological cancers, and they overcome immunosuppressive effects of tumor microenvironment. We developed a mathematical model to address the question of how the density of NK cells affects the growth of the tumor. We found that the antitumor efficacy increases when the endogenous NKs are depleted and also when exogenous NK cells are injected into the tumor. These predictions were validated by our in vivo and in vitro experiments.