Cannabidiol (CBD) in Dietary Supplements: Perspectives on Science, Safety, and Potential Regulatory Approaches.

The proliferation in the last few years of cannabidiol (CBD)-containing products in the U.S. markets has been greatly accelerated by changes in the regulatory environment, and by perceptions of their health benefits and presumed safety. The result has been aggressive marketing of many types of products, some of dubious quality, making or implying drug-type claims. The recent approval by the U.S. Food and Drug Administration (FDA) of CBD in the form of Epidiolex®, further complicates the regulatory picture. In addition, a number of studies suggest that, at least at high doses, there may be serious adverse effects or drug interactions associated with CBD. At present, CBD-containing products do not meet the strict definition of dietary supplements, but the FDA is continuing to consider some framework under which they might be allowed. Meanwhile, FDA has adopted a "risk-based" enforcement policy. Possible approaches to a new framework for regulation of CBD products as dietary supplements are discussed here, including expanded research emphasis, a robust corporate stewardship program, and a rigorous adverse event reporting program.

Perioperative Outcomes and Complications After Primary Total Hip Arthroplasty in Patients With Disproportionately Short Stature: A Matched Cohort Analysis.

BACKGROUND: This study compared (1) perioperative outcomes, (2) postoperative complications, and (3) reoperation rates after primary total hip arthroplasty (THA) between short stature patients and matched control patients. METHODS: A review of primary THA patients from 2012 to 2017 using an institutional database was conducted. This yielded 12,850 patients of which 108 were shorter than 148 cm. These patients were matched 1:1 by age (P = .527), gender (P = .664), and body mass index (P = .240) to controls. The final study population with minimum 1-year follow-up that was included for analysis comprised 47 patients in the short stature cohort and 57 patients in the control cohort. The following outcomes/complications were compared: operative times, lengths of stay (LOSs), intraoperative fractures, minor complications, 90-day readmissions, and revisions. RESULTS: Operative times were significantly longer in the short stature cohort than in the matched control cohort (133 ± 65 minutes vs 104 ± 30 minutes, P = .005). In addition, hospital LOS was slightly longer in the short stature group than in the matched control groups (3.2 ± 1.5 days vs 2.6 ± 1.0, P = .017). Rates of intraoperative fractures (P = 1.000), minor complications P = .406), 90-day readmissions (P = .5000), and revision (P = .202) were similar between the short stature and control cohorts. CONCLUSION: Patients with disproportionately short stature had longer operative times and slight longer LOS. However, complication and readmission rates were similar. Future studies with larger sample sizes are warranted to confirm these findings and further evaluate implant survivorship in this unique THA patient population.

Vertical shear pelvic injury: evaluation, management, and fixation strategies.

Vertical shear pelvic ring fractures are rare and account for less than 1% of all fractures. Unlike severely displaced antero-posterior compression and lateral compression pelvic fractures, patients' mortality is lower. Nevertheless, patients must be managed acutely using well-defined ATLS protocols and institution-specific protocols for haemodynamically unstable pelvic ring fractures. The definitive treatment of vertical shear pelvic fractures is however more controversial with a paucity of literature to recommend the ideal reduction and fixation strategy. While the majority of injuries can be reduced and fixed in a closed manner, orthopaedic traumatologists should be familiar with the contraindications to those techniques as well as options such as tension band plating and lumbo pelvic fixation. Our paper reviews the acute management, associated injuries and definitive reduction and fixation strategies of vertical shear pelvic fractures. In addition, we propose a treatment algorithm for the selection of the most appropriate fixation technique.

Root Cause Analysis and Actions for the Prevention of Medical Errors: Quality Improvement and Resident Education.

The quality of care delivered by orthopedic surgeons continues to grow in importance. Multiple orthopedic programs, organizations, and committees have been created to measure the quality of surgical care and reduce the incidence of medical adverse events. Structured root cause analysis and actions (RCA2) has become an area of interest. If performed thoroughly, RCA2 has been shown to reduce surgical errors across many subspecialties. The Accreditation Council for Graduate Medical Education has a new mandate for programs to involve residents in quality improvement processes. Resident engagement in the RCA2 process has the dual benefit of educating trainees in patient safety and producing meaningful changes to patient care that may not occur with traditional quality improvement initiatives. The RCA2 process described in this article can provide a model for the development of quality improvement programs. In this article, the authors discuss the history and methods of the RCA2 process, provide a stepwise approach, and give a case example. [Orthopedics. 2017; 40(4):e628-e635.].

Data Sharing Between Providers and Quality Initiatives Eliminate Unnecessary Nursing Home Admissions.

BACKGROUND: The Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) has monitored discharge disposition, after total hip and knee arthroplasties, since inception in 2012 and found the standardized risk of extended care facility (ECF) placement to be highly variable between hospitals. METHODS: The variation in standardized risks of ECF placement among MARCQI member sites was reported to the collaborative. At the May 2, 2014 quarterly meeting, a quality initiative was started, emphasizing the wide variability between hospitals, the contribution of hospital and surgeon to that variability using median odds ratios, and the need for outlier hospitals to initiate quality improvement (QI) processes. Patients from 29 hospitals that were members of MARCQI before the intervention were included in this analysis. We compared standardized risks before and after the intervention in the entire cohort, and for 3 hospitals that implemented institution-specific QI projects. We report changes in ECF placement, length of stay, emergency room visits, and readmissions over time. RESULTS: This study includes 31,347 patients before and 20,879 patients after the implementation of the quality initiative. The range in standardized risk dropped from 9.4%-46.1% to 9.4%-32.4% and the average dropped from 23.0% to 19.6%. Three outlier hospitals decreased their absolute risk of ECF placement by 12.2%, 8.9%, and 12.4% after QI, without increases in adverse outcomes. CONCLUSION: Discharge to ECF after primary hip and knee arthroplasties is highly variable and influenced by hospital and surgeon practices. Hospital-level QI measures can decrease ECF admissions.

Previous arthroscopic repair of femoro-acetabular impingement does not affect outcomes of total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is commonly elected following failed arthroscopic treatment of femoro-acetabular impingement (FAI). The purpose of this study was to evaluate post-operative outcomes of primary THA in patients who had previously undergone arthroscopic treatment for FAI. METHODS: A retrospective, matched case-control study was conducted. The case group included 39 patients who underwent THA after previous hip arthroscopy for FAI. Thirty-nine patients who had a primary THA without previous hip arthroscopy served as a control group and were matched for age, sex and body mass index. Surgical outcomes were assessed based on inpatient hospital metrics and outpatient complication measures. Statistical analyses were performed to identify the significance of outcome variables between case and control groups. RESULTS: No statistically significant differences were observed between groups in terms of operative time, haemoglobin drop, intra-operative estimated blood loss, transfusion requirements, amounts of opioids provided, functional mobility assessments on post-operative days one and two, length of hospitalization, discharge location, emergency department visits, post-operative superficial or deep periprosthetic infection, revision rates for dislocation or formation of heterotopic bone (p-values = 0.1-0.8). A statistically significant difference was found between the walking scores on the third post-operative day (p = 0.015). CONCLUSIONS: These findings, while underpowered, are consistent with other previously published reports. Previous hip arthroscopy for FAI does not appear to impact post-operative outcomes of a subsequent THA. Larger datasets from different surgeons and centers are needed to further assess these conclusions. LEVEL OF EVIDENCE: Case-control level-III.

How to perform a root cause analysis for workup and future prevention of medical errors: a review.

Providing quality patient care is a basic tenant of medical and surgical practice. Multiple orthopaedic programs, including The Patient Safety Committee of the American Academy of Orthopaedic Surgeons (AAOS), have been implemented to measure quality of surgical care, as well as reduce the incidence of medical errors. Structured Root Cause Analysis (RCA) has become a recent area of interest and, if performed thoroughly, has been shown to reduce surgical errors across many subspecialties. There is a paucity of literature on how the process of a RCA can be effectively implemented. The current review was designed to provide a structured approach on how to conduct a formal root cause analysis. Utilization of this methodology may be effective in the prevention of medical errors.

The subscapularis-sparing approach in humeral head replacement.

BACKGROUND: This report represents a prospective case series evaluating an open deltopectoral approach, both radiologically and clinically, without tenotomy or complete takedown of the subscapularis tendon insertion. We hypothesized that this novel technical approach would allow preservation of the upper tendon border, thus decreasing subscapularis repair failures and fatty infiltration while simultaneously allowing accelerated rehabilitation. METHODS: Fifty patients underwent humeral head replacement surgery through a subscapularis-sparing approach. In this approach, we take down only the inferior 30% to 50% of the subscapularis tendon, leaving the critical superior aspect of the tendon attached to the lesser tuberosity. Forty-three patients were included in the postoperative results (7 were lost to follow-up). Nineteen patients had a postoperative magnetic resonance imaging study, and 24 patients had ultrasound evaluation. Physical examination included belly-press and lift-off tests; follow-up included visual analog scale, American Shoulder and Elbow Surgeons, Constant, modified UCLA, Rowe, and Short Form 12 scores. RESULTS: All patients had a minimum 2-year follow-up. All patients had subscapularis strength equal to the opposite side as measured by lift-off, belly-press, and bear hug tests. Average postoperative scores all showed statistically significant improvement except for general health. All had an intact subscapularis tendon attachment as evaluated by either magnetic resonance imaging or ultrasound imaging. None had atrophy in the muscle belly. CONCLUSIONS: The subscapularis-sparing, minimally invasive approach to the glenohumeral joint provides adequate exposure to allow humeral head replacement. When the upper border of the subscapularis insertion is left intact, there is a decreased risk of postoperative failure (rupture or atrophy) of the subscapularis tendon.

Surface Replacement Arthroplasty of the Humeral Head in Young, Active Patients: Midterm Results.

BACKGROUND: The treatment of glenohumeral arthritis in young, active patients remains controversial. Standard total shoulder arthroplasty in this patient group has not obtained the same satisfaction rate as in older patients. One surgical option that has emerged is humeral resurfacing. HYPOTHESIS: Humeral head surface replacement arthroplasty (SRA) would provide satisfactory clinical outcomes in active patients, allowing them to maintain their normal lifestyle without activity restrictions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From 2004 to 2007, all consecutive surface replacement arthroplasties of the humerus performed at the authors' institution were identified and retrospectively reviewed, and 118 patients who underwent SRA during this time were identified. This study included patients younger than 60 years who wished to maintain an active lifestyle; 52 of the 118 patients met the inclusion criteria. University of California at Los Angeles (UCLA) shoulder scores and subjective shoulder value (SSV) scores were used to measure clinical outcomes at an average follow-up of 6 years (range, 4-8 years). Of the 52 patients meeting the inclusion criteria, 48 were contacted and examined for the study, with 4 patients lost to follow-up. RESULTS: The mean postoperative UCLA score was 28.03, with 1 patient requiring revision because of pain and glenoid wear. The mean SSV was 92% (range, 0%-100%), with 3 patients restricting their activity because of the shoulder. Forty-seven of the 48 contacted patients stated that, given the option, they would have the same surgery again. One patient required revision surgery because of pain. CONCLUSION: Surface replacement arthroplasty provided reasonable results in patients younger than 60 years with high activity demands with a low rate of revision at midterm follow-up.

Synthesis and characterization of an anti-apoptotic immunosuppressive compound for improving the outcome of islet transplantation.

Mycophenolic acid (MPA) is a commonly used immunosuppressive drug for human islet transplantation. However, it is toxic to transplanted islets, causing primary nonfunction. We recently synthesized a quinic acid derivative, 1,3,4,5-tetrahydroxy-N-propylcyclohexanecarboxamide (KZ41), which has anti-inflammatory and anti-apoptotic effects. We hypothesized that the conjugate (E)-2,3,5-trihydroxy-5-(propylcarbamoyl) cyclohexyl 6-(4-ethoxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate (JP-3-110), which is composed of KZ41 and MPA through esterification, can suppress the immune rejection while inducing less toxicity. Early characterization showed that the solubility of JP-3-110 was significantly higher than that of MPA, though JP-3-110 was still poorly water-soluble. The ester bond connecting KZ41 and MPA is stable for a limited duration (<4 weeks). Pharmacological studies demonstrated that JP-3-110 induced significantly less activated caspase 3 and apoptotic cell death of human islets than MPA, while maintaining an equally potent immunosuppressive effect. A similar immunosuppressive effect of JP-3-110 and MPA in humanized NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NOD scid gamma, NSG) mice with adoptively transferred human immunity was observed. Taken together, our results demonstrated that JP-3-110 can be a safer immunosuppressive agent for human islet transplantation.

Middle ear effusion in adult ICU patients: a cohort study.

We conducted a prospective study of 74 adults-34 men and 40 women, aged 18 to 90 (mean: 60.2)-to determine the prevalence of middle ear effusion (MEE) among patients in the setting of an intensive care unit (ICU) and to compare the findings with those of a control group of non-ICU hospitalized patients. Other goals were to identify risk factors associated with MEE in ICU patients and to evaluate any association with fever. Both groups included 37 patients. MEE was present in 19 patients (51.4%) in the ICU group, compared with only 2 patients (5.4%) in the control group (p < 0.01; odds ratio: 18.5; 95% confidence interval: 3.9 to 88.3). In the ICU group, there were statistically significant associations between MEE and both the use of mechanical ventilation (p = 0.03) and the use of sedation (p = 0.02). No significant relationships were seen in terms of length of stay, body position, the use of an endotracheal tube, the length of ventilation, and the use of a feeding tube. Fever was present in 8 ICU patients (21.6%) and 3 controls (8.1%), but none of the fevers was associated with MEE. We conclude that adult ICU patients have a high prevalence of MEE (51.4% in our sample) that is perhaps unrecognized. We believe that MEE in these patients is most likely related to altered consciousness, sedation, and mechanical ventilation. MEE was an unlikely cause of fever.

EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in vivo.

To investigate the effectiveness of EDL-291, a 6,7-dimethoxy-1-[4-(4-methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline dihydrochloride compound, in inhibiting the survival of glioblastoma in vitro and in vivo. Dose-response curves were generated to determine the EC50 in rat and human glioblastoma cell lines by treatment with different dilutions of EDL-291. To evaluate the architecture of the glioblastoma cells after treatment with EDL-291, the rat and human glioblastoma cells were stained with Mito Tracker Green FM. To determine whether autophagy was induced in EDL-291-treated glioblastoma cells, both rat and human glioblastoma cell lines were stained with acridine orange and light chain-3 immunoblots were performed. The efficacy of EDL-291 was monitored in vivo using a rat glioblastoma model. Rat glioblastoma cells were transplanted into an intracranial rat model, followed by infusions of saline, a low dose of EDL-291 (20 mg/kg for the first half hour, followed by 40 mg/kg EDL-291 in saline for 4 h), or a high dose of EDL-291 (60 mg/kg for the first half hour, followed by 90 mg/kg EDL-291 for 4 h). EDL-291 inhibits glioblastoma in vitro by destroying the mitochondria as shown with Mito Tracker Green FM. Acridine orange staining and light chain-3 immunoblots suggest that autophagy is induced when glioblastoma cells are treated with EDL-291. In vivo, a low dosage of EDL-291 is sufficient and effective in reducing glioblastoma tumor size. EDL-291 selectively induces cell death in rat and human glioblastoma cell lines by the induction of autophagy. EDL-291 exhibits antiglioblastoma effects both in vitro and in vivo.