Radiographic Prediction of Soft Tissue Injury Associated with Tibial Plateau Fractures: The Direction of Articular Depression Matters.

This investigation aimed to evaluate the impact of coronal articular fragment displacement of Schatzker type II tibial plateau fractures on concomitant soft tissue knee injuries. One hundred consecutively treated patients were included. Depression depth and coronal articular fragment displacement were measured radiographically, and medial collateral ligament (MCL) and lateral meniscus (LM) injury, and pain and range of motion (ROM) on final follow up, were recorded. Multivariable regression was then performed. Coronal articular fragment displacement was medially and laterally hinged in 74% and 26% of patients, respectively. MCL injuries were significantly higher in the lateral hinge group (odds ratio [OR]: 3.25; confidence interval [CI]: 1.07 to 9.84; p = 0.03). No difference was found in LM injury incidence and amount of articular depression between groups. At final follow-up, average pain and ROM was similar between groups. Findings demonstrate a significant correlation between laterally hinged articular depression in Schatzker II tibial plateau fractures and concomitant MCL injury. (Journal of Surgical Orthopaedic Advances 32(4):270-275, 2023).

Key Evidence Supporting Prescription Opioids Approved by the U.S. Food and Drug Administration, 1997 to 2018.

BACKGROUND: Little is known about the evidence required by the U.S. Food and Drug Administration (FDA) for new approvals of opioid analgesics. OBJECTIVE: To characterize the quality of safety and efficacy data in new drug applications (NDAs) for opioid analgesics approved by the FDA between 1997 and 2018. DESIGN: Cross-sectional analysis. SETTING: Data from ClinicalTrials.gov, FDA reviews, and peer-reviewed publications. PARTICIPANTS: Patients with pain who participated in phase 3 pivotal trials. INTERVENTION: FDA-approved opioid analgesics. MEASUREMENTS: Key characteristics of each NDA, including the number, size, and duration of pivotal trials; trial control groups; the use of enriched trial populations; and systematically measured safety outcomes. RESULTS: Most of the 48 NDAs evaluated were for new dosage forms (n = 25 [52.1%]) or new formulations (n = 9 [18.8%]); only 1 (2.1%) was for a new molecular entity. Of 39 NDAs approved for treating chronic pain, only 21 products were supported by at least 1 pivotal trial; these trials (n = 28) had a median duration of 84 days (interquartile range [IQR], 25 to 84 days) and enrolled a median of 299 patients (IQR, 174 to 525 patients). Seventeen (81%) of these products were approved on the basis of designs that excluded patients who could not tolerate the drugs, had early adverse effects, or reported few immediate benefits. Among NDAs for chronic pain, 8 (20.5%) included pooled safety reviews that reported systematic assessment of diversion, 7 (17.9%) reported systematic measurement of nonmedical use, and 15 (38.5%) assessed development of tolerance. Eight of 9 products for acute pain were supported by at least 1 pivotal trial; the pivotal trials (n = 19) had a median duration of 1 day (IQR, 1 to 2 days) and enrolled a median of 329 patients (IQR, 199 to 456 patients). Although all but 1 of the 48 approved NDAs were for previously approved moieties, analysis of available NDAs for referent products yielded similar findings. LIMITATIONS: The analysis was limited to approved opioids. Animal studies and nonpivotal trials were excluded. Evidence for safety in NDAs was presented for chronic pain only. CONCLUSION: Between 1997 and 2018, the FDA approved opioids on the basis of pivotal trials of short or intermediate duration, often in narrowly defined pain populations of patients who could tolerate the drug. Systematic collation of certain important safety outcomes was rare. PRIMARY FUNDING SOURCE: None.

Estimated costs of pivotal trials for U.S. Food and Drug Administration-approved cancer drugs, 2015-2017.

BACKGROUND: Pivotal clinical trials provide critical evidence to regulators regarding a product's suitability for marketing approval. The objectives of this study are (1) to characterize select features of trials for oncology products approved by the U.S. Food and Drug Administration between 2015 and 2017; and (2) to quantify the costs of these trials and how such costs varied based on trial characteristics. METHODS: We identified novel oncology therapeutic drugs, and their respective pivotal trials, approved between 2015 and 2017 using annual summary reports from the Food and Drug Administration. Cost estimates for each pivotal trial were calculated using IQVIA's CostPro, a clinical trial cost estimating tool based on executed contracts between pharmaceutical manufacturers and contract research organizations. Measures of drug and trial characteristics included trial design, end point, patient enrollment, and regulatory pathway. We also performed sensitivity analyses that varied assumptions regarding how efficiently each trial was conducted. RESULTS: A total of 39 pivotal clinical trials provided the basis for Food and Drug Administration approval of 30 new oncology drugs from 2015 to 2017. Among these trials, primary end points were objective response rate in 20 (51.3%), progression-free survival in 13 (33.3%), and overall survival in 6 (15.4%). Twenty trials (51.3%) were single-arm studies. The median estimated cost of oncology pivotal trials was $31.7 million (interquartile range = $17.0-$60.4 million). Trials with objective response rate as primary end point had a median estimate of $17.7 million (interquartile range = $11.9-$27.1 million), compared with trials examining progression-free survival ($42.3 million, interquartile range = $34.6-$101.2 million) or overall survival ($79.4 million, interquartile range = $56.9-$97.7 million) (p < 0.001). Estimated costs for single-arm trials ($17.7 million, interquartile range = $11.9-$23.7 million) were less than for trials with a placebo-controlled ($56.7 million, interquartile range = $40.9-$103.9 million) or active control arm ($67.6 million, IQR = $35.5-$93.5 million) (p < 0.001). CONCLUSIONS: Relative to the estimated costs of drug development, the costs of these oncology pivotal trials were modest, with trials that produced more valuable scientific information costing more than their counterparts.

Globalization of clinical trials: Variation in estimated regional costs of pivotal trials, 2015-2016.

BACKGROUND/AIMS: Despite the increasing globalization of clinical trials, little is known regarding how the trial site costs vary around the world. We quantified the geographical distribution and regional cost differences for the clinical trials that established the benefits for new therapeutic drugs approved by the US Food and Drug Administration in 2015 and 2016. METHODS: We included all pivotal clinical trials for 59 new molecular entities approved by the US Food and Drug Administration in 2015 and 2016 that included at least one site in North America. We derived cost estimates from IQVIA's CostPro, a global clinical trial cost-estimating tool used by pharmaceutical sponsors. We assessed the patient and site allocation of these trials across eight geographic regions. To quantify the region-specific cost differences, we conducted a within-trial comparison by expressing the estimated regional costs associated with the sites in each global region as a percent of the same costs in North America. We also estimated the percentage breakdown of regional cost components (pass-through, site management, regulatory, and study conduct costs) for each trial and for all endpoints reported the median and interquartile range. RESULTS: Overall, 127 pivotal clinical trials enrolled 91,415 patients from 13,264 sites. Most patients (60.3%) and sites (57.3%) were outside North America. A median of 66% of the total estimated trial costs (interquartile range: 60%-72%) were spent on regional tasks, with the largest share (53.3%) going directly to trial sites and the remainder going to other regional trial management tasks. Differences were greatest in four lower cost regions: Africa, with an estimated regional cost per site of 49% of North America (interquartile range: 44%-56%), Central Europe 50% (interquartile range: 41%-63%), Middle East 53% (interquartile range: 42%-64%) and Latin America 59% (interquartile range: 50%-70%). Overall, 90 (71%) of the 127 pivotal trials had a total of 3160 sites in these lower cost regions. In contrast, savings were more limited in Western Europe, Oceania, and Asia, where estimated regional costs were 78% of North America (interquartile range: 67%-89%). One-quarter of the trials with sites in Asia and Oceana did not achieve cost savings in those regions relative to North America. CONCLUSION: Among this sample of pivotal trials for recently approved US Food and Drug Administration products, most patients and sites enrolled were outside of North America, with selection of regional sites having a significant impact on total trial costs.

Motorized scooter injuries in the era of scooter-shares: A review of the national electronic surveillance system.

INTRODUCTION: There has been a spike in recent news regarding motorized scooter injuries due to the expansion of scooter sharing companies. Given the paucity of literature on this topic, the purpose of our study was to describe and quantify emergency department encounters associated with motorized scooter related injuries. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried for motorized scooter related injuries from 2013 to 2017. Patient demographics, diagnosis, injury location, narrative description of incident, and disposition data were collected from emergency department encounters. RESULTS: There were an estimated 32,400 motorized scooter injuries from 2013 to 2017. The estimated incidence did not change significantly over time with 1.9 cases per 100,000 in 2013 and 2.6 cases per 100,000 in 2017. A 77.0% increase in scooter injuries was noted for millennials from 2016 to 2017. Head injuries were the most common body area injured (27.6%). Fractures or dislocations (25.9%) were the most common diagnosis. The most common site of fracture was the wrist and lower arm (35.4%). There were no deaths. Major orthopaedic injury and concussion were the strongest independent predictors of hospital admission. CONCLUSIONS: Head injuries were the most commonly injured body part, while fractures or dislocations were the most common diagnosis. These results highlight the importance of using protective equipment while riding motorized scooters, and lay a foundation for future policies requiring helmet use.

CT can stratify patients as low risk for tibial neuropathy following a talus fracture.

OBJECTIVE: Determine the incidence of tibial neuropathy following talus fractures and CT's ability to stratify patients at risk for developing post-traumatic neuropathy. MATERIALS AND METHODS: In this IRB-approved retrospective analysis, 71 talus fractures and 8 contralateral control ankle CTs were reviewed by one observer blinded to clinical information. CT evidence suggestive of tibial neurovascular bundle injury included nerve displacement, perineural fat effacement/edema, and bone touching nerve. The association between these CT findings and clinically evident tibial neuropathy was analyzed. A semi-quantitative likelihood score was assigned based on the degree of the CT findings around the nerve. Interobserver agreement was calculated between 2 other readers. RESULTS: Twenty-five percent of patients in this cohort had clinical evidence of tibial neuropathy. There was a high specificity (0.87-0.93) and negative predictive value (0.83-0.87), a moderate accuracy (0.80-0.82), but a lower sensitivity (0.33-0.56) associated with the CT findings. Among the CT findings, nerve displacement (p < 0.0001) and bone touching nerve (p = 0.01) were associated with tibial neuropathy. A likelihood score of 2-5 was associated (p = 0.007-0.015) with tibial neuropathy. The presence of tibial neuropathy and nerve recovery were not associated with hospital length of stay, while CT findings were. There was substantial agreement between the three readers: likelihood scores 2+ (k = 0.78) and 3+ (k = 0.72). CONCLUSIONS: Tibial neuropathy occurs following talus fractures, and CT findings may help surgeons narrow down the number of patients requiring close neurological follow-up.

Completeness of serious adverse drug event reports received by the US Food and Drug Administration in 2014.

PURPOSE: Adverse drug event reports to the US Food and Drug Administration (FDA) remain the primary tool for identifying serious drug adverse effects without adequate existing warnings. We assessed the completeness of reports the FDA received in 2014. METHODS: Serious adverse drug event reports were evaluated for whether they included age, gender, event date, and at least one medical term describing the event in computer excerpts. Report sources were direct reports to the FDA, manufacturer expedited reports about events without adequate warnings, and manufacturer periodic reports about events with existing warnings. RESULTS: In 2014, the FDA received 528,192 new case reports indicating a serious or fatal outcome, 25,038 (4.7%) directly from health professionals and consumers, and 503,154 (95.3%) from drug manufacturers. Overall, 21,595 (86.2%) of serious reports submitted directly to the FDA provided data for all four completeness variables, compared with 271,022 (40.4%) of manufacturer expedited reports and 24,988 (51.3%) of periodic reports. Among manufacturer serious reports, 37.9% lacked age and 46.9% had no event date. Performance by 25 manufacturers submitting 5000 or more reports varied from 24.4% complete on all variables to 67% complete. Patient death cases had the lowest completeness scores in all categories. CONCLUSIONS: By these measures, report completeness from drug manufacturers was poor compared with direct submissions to the agency. The FDA needs to update reporting requirements and compliance policies to help industry capture better adverse event information from new forms of manufacturer interactions with health professionals and consumers. Copyright © 2016 John Wiley & Sons, Ltd.

Underrepresentation of black individuals in pivotal trials for novel anticancer drugs: Potential consequence of using estimated creatinine clearance to assess kidney function?

BACKGROUND: Black individuals are historically underrepresented in oncology clinical trials. One potential reason for this is the prevalence of kidney disease in Black individuals, utilization of estimated creatinine clearance as a surrogate for glomerular filtration rate (GFR) in oncology, and GFR-based trial eligibility criteria. We characterized the representation of racial minorities in anticancer agent pivotal trials and examined if GFR-based trial eligibility criteria impact the proportion of Black individuals in trial populations. METHODS: We constructed a data repository for anticancer drugs FDA-approved from 2015 to 2019 and associated pivotal trials, from which we extracted trial population racial compositions and GFR-based trial eligibility criteria. We calculated the participation-to-incidence ratio (PIR) and participation-to-mortality ratio (PMR) for a variety of cancer sites, where PIR or PMR >1.2 and <0.8 indicate overrepresentation and underrepresentation, respectively. We evaluated the relationship between GFR eligibility cutoffs and the proportion of Black enrollees with Spearman rank correlation coefficient. RESULTS: We assessed 24,698 patients in 74 trials. Black individuals were underrepresented in all trials (PIR ≤0.48, PMR ≤0.50). For trials with GFR-based eligibility criteria (n = 49), a lower GFR cutoff was modestly associated with a higher proportion of Black enrollees (r = -0.29, p = 0.039). This relationship was strengthened for trials that only used estimated creatinine clearance to estimate GFR (r = -0.43, p = 0.004). CONCLUSIONS: GFR-related eligibility, and specifically the use of estimated creatinine clearance, may contribute to Black individuals being disproportionately excluded from cancer clinical trials. This highlights the need for implementation of contemporary GFR equations and other interventions to boost racial minority trial enrollment.

Incidence and Risk Factors of Heterotopic Ossification in the Knee After Reamed Tibial Nailing.

INTRODUCTION: Heterotopic ossification (HO) in the knee after tibial intramedullary nailing (IMN) has yet to be thoroughly investigated. Our aim was to assess frequency and associated factors for HO in the knee after tibial IMN. METHODS: This is a retrospective review at a single level 1 urban trauma center of 213 patients who underwent reamed tibial IMN. Plain radiographs were reviewed postoperatively and on final follow-up (≥6 weeks). Chart review was performed for surgical approach (suprapatellar versus infrapatellar), demographics, injury characteristics, and clinical follow-up. The primary outcome was frequency of HO. RESULTS: HO on final follow-up (mean: 41.43 weeks) was recorded in 15% cases. Postsurgical retroinfrapatellar reaming debris (odds ratio [OR], 4.73), Injury Severity Score (OR, 1.05), intensive care unit admission (OR, 2.89), chest injury (OR, 3.4), and ipsilateral retrograde femoral IMN (OR, 5.08) showed a notable association with HO development. No association was observed in HO formation between surgical approach, knee pain, or range-of-motion deficits. DISCUSSION: Radiographic evidence of HO in the knee after reamed tibial IMN is not uncommon and is associated with retained reaming debris, Injury Severity Score, chest injury, intensive care unit admission, and ipsilateral retrograde femoral nailing. No differences were noted in HO formation between approaches. HO was not associated with knee pain or range-of-motion deficits.

Relationship between near infrared spectroscopy and intra-compartmental pressures.

BACKGROUND: Near infrared spectroscopy (NIRS) has been suggested as a possible means for detecting perfusion deficits in patients with acute compartment syndrome (ACS). STUDY OBJECTIVES: To longitudinally examine NIRS in an ACS model to determine its responsiveness to decreasing perfusion pressure. METHODS: A NIRS sensor pad was placed under a tourniquet over the anterior compartment in the mid-tibia region on 20 volunteers. Initial perfusion pressures and NIRS values were recorded. The tourniquet pressure was sequentially raised by 10 mm Hg in 10-min intervals until systolic pressure was surpassed. NIRS values and perfusion pressure were determined at the end of each 10-min interval. RESULTS: There was no change in mean NIRS values from the initial baseline until 30 mm Hg of perfusion pressure was reached. Additionally, a statistically significant drop in mean NIRS values was observed as perfusion pressures dropped from 10 mm Hg to 0 mm Hg, and again with subsequent decreases of 10 mm Hg perfusion pressure until systolic pressure was surpassed. CONCLUSIONS: These results coincide with previously published studies using alternative methods of measuring blood flow or perfusion. NIRS values were responsive to decreasing perfusion pressures over a longitudinal period of time in an ACS model. These results suggest that NIRS may be useful for continuous, non-invasive monitoring of patients for whom ACS is a concern. Additional studies on traumatized patients are required.

Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis.

OBJECTIVE: Examine patterns of adult medical use of amphetamine and methylphenidate stimulant drugs, classified in the USA as Schedule II controlled substances with a high potential for psychological or physical dependence. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Prescription drug claims for US adults, age 19-64 years, included in a commercial insurance claims database with 9.1 million continuously enrolled adults from 1 October 2019, through 31 December 2020. Stimulant use was defined as adults filling one or more stimulant prescriptions during calendar 2020. OUTCOME MEASURES: The primary outcome was an outpatient prescription claim, service date and days' supply for central nervous system (CNS)-active drugs. Combination-2 was defined as 60 days or more of combination treatment with a Schedule II stimulant and one or more additional CNS-active drugs. Combination-3 therapy was defined as the addition of 2 or more additional CNS-active drugs. Using service date and days' supply, we examined the number of stimulant and other CNS-active drugs for each of the 366 days of 2020. RESULTS: Among 9 141 877 continuously enrolled adults, the study identified 276 223 individuals (3.0%) using Schedule II stimulants during 2020. They filled a median of 8 (IQR, 4-11) prescriptions for these stimulant drugs that provided 227 (IQR, 110-322) treatment days of exposure. Among this group, 125 781 (45.5%) combined use of one or more additional CNS active drugs for a median of 213 (IQR, 126-301) treatment days. Also, 66 996 (24.3%) stimulant users used two or more additional CNS-active drugs for a median of 182 (IQR, 108-276) days. Among stimulants users, 131 485 (47.6%) were exposed to an antidepressant, 85 166 (30.8%) filled prescriptions for anxiety/sedative/hypnotic medications and 54 035 (19.6%) received opioid prescriptions. CONCLUSION: A large proportion of adults using Schedule II stimulants are simultaneously exposed to one or more other CNS-active drugs, many with tolerance, withdrawal effects or potential for non-medical use. There are no approved indications and limited clinical trial testing of these multi-drug combinations, and discontinuation may be challenging.

Inclusion of Participants with CKD and Other Kidney-Related Considerations during Clinical Drug Development: Landscape Analysis of Anticancer Agents Approved from 2015 to 2019.

BACKGROUND: The US Food and Drug Administration has prioritized efforts to expand availability of therapies, including anticancer agents, for patients with CKD. US Food and Drug Administration Guidance recommends inclusion of study participants with CKD in clinical trials, improving pharmacokinetic characterization in people with decreased GFR, and using contemporary GFR assessment methods during drug development. We performed a landscape analysis of anticancer agents approved from 2015 to 2019 to evaluate inclusion of study participants with CKD and GFR assessment methods used during drug development and subsequent translation to kidney-related safety and dosing data in product labeling. METHODS: Oncology drugs approved from 2015 to 2019 and associated pivotal trials were identified. We evaluated inclusion of study participants with CKD in pivotal trials and pharmacokinetic analyses, investigated GFR assessment methods used for pivotal trial eligibility and renal pharmacokinetic analyses, and identified kidney-related adverse drug event and dosing information. RESULTS: A total of 55 drugs and 74 pivotal trials were included. Of the pivotal trials, 95% contained kidney-related eligibility criteria, including 68% with GFR-based eligibility. The median lower limit of GFR required for inclusion was 45 ml/min or ml/min per 1.73 m 2 . Pharmacokinetic analyses were performed in CKD stages 4-5 and hemodialysis for only 29% and 6% of drugs, respectively. Estimated creatinine clearance was used in over 60% and 80% of pivotal trials and pharmacokinetic analyses, respectively. Reporting of kidney-related adverse drug events was highly variable. Product labeling for 49% of drugs contained no kidney dosing information. CONCLUSIONS: Study participants with CKD continue to be excluded from anticancer drug development, and GFR estimation in pivotal trials and renal pharmacokinetic analyses remains imprecise and heterogeneous. Furthermore, kidney-related safety and dosing information is scarcely and inconsistently presented.

Underreporting of hemorrhagic and thrombotic complications of pharmaceuticals to the U.S. Food and Drug Administration: empirical findings for warfarin, clopidogrel, ticlopidine, and thalidomide from the Southern Network on Adverse Reactions (SONAR).

The U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS), familiarly known as "MedWatch," is the nation's primary tool for postmarket pharmaceutical safety surveillance. This system relies on adverse events voluntarily reported by health care providers and consumers either directly to the FDA or to drug manufacturers, which are required to prepare and forward the information to the agency. Little is known about how frequently adverse events are reported. Previous estimates range from 1 to 31% depending on the event, drug, and time period. We used published incidence studies to calculate reporting rates for hemorrhage, emergency hospitalization, and venous thromboembolism (VTE) associated with four drugs. We estimated annual reporting rates of 1.07% for 33,171 emergency hospitalizations of patients older than 65 years associated with warfarin, 0.9% for 13,363 hospitalizations of clopidogrel and ticlopidine, and 1.02% for an estimated 67,200 hemorrhage cases associated with warfarin. We also estimated a 9-year reporting rate of 2.3% for VTE associated with thalidomide. The incidence of these hematologic adverse drug events is high and reporting rates are low, and near the lower boundary of the 1 to 15% range seen for other events.

CD4 count is associated with postoperative infection in patients with orthopaedic trauma who are HIV positive.

BACKGROUND: Since the advent of effective antiretroviral therapy, the number of people with AIDS has increased and a certain percentage of these patients will require emergent orthopaedic surgery. Little is known regarding orthopaedic infections and the association of CD4 counts with postoperative infection in patients with HIV infection who experience orthopaedic trauma. QUESTIONS/PURPOSES: We questioned whether the postoperative infection rate is higher after orthopaedic trauma surgery for patients who are HIV positive than for patients who are HIV negative undergoing similar surgery and aimed to identify preoperative variables that may be important in predicting postoperative infection in patients who are HIV positive. METHODS: We determined the postoperative infection rate in 64 patients who were HIV positive and who underwent orthopaedic surgery requiring instrumentation or an implant from January 2001 to May 2007. We compared this rate with historical control data from 2003 to 2007 for all orthopaedic procedures at Grady Memorial Hospital. We examined numerous preoperative variables for association with postoperative infection, including CD4 count, length of inpatient stay, polytrauma, and malnutrition. RESULTS: Of the 64 patients, 15 had postoperative infections develop with an infection rate of 23%, compared with the 3.9% rate for the historical control subjects. Analysis of the 64 patients who were HIV positive revealed CD4 counts less than 300 were associated with development of postoperative infection. Hospital stay, polytrauma, and low serum albumin also were found to be associated with postoperative infection. CONCLUSIONS: It is evident that patients who are HIV positive with low CD4 counts undergoing emergent orthopaedic intervention are a patient population at risk for infection. Further study is necessary to evaluate preoperative and perioperative interventions that may decrease infections in this population. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Safety and effectiveness of NMDA receptor antagonists for depression: A multidisciplinary review.

Ketamine, an anesthetic available since 1970, and esketamine, its newer S-enantiomer, provide a novel approach for the treatment of depression and other psychiatric disorders. At subanesthetic doses, the two drugs, along with their older congener, phencyclidine (PCP), induce a transient, altered mental state by blocking the N-methyl-D-aspartate (NMDA) receptor for glutamate, the primary excitatory neurotransmitter in the mammalian central nervous system. This multidisciplinary review examines the pharmacology/direct effects on consciousness, effectiveness in depression and acute suicidality, and safety of these fast-acting NMDA antagonists. To capture the essence of 60 years of peer-reviewed literature, we used a semi-structured approach to the subtopics, each of which required a different search strategy. We review the evidence for the three primary reported benefits of the two clinical drugs when used for depression: success in difficult-to-treat patients, rapid onset of action within a day, and immediate effects on suicidality. Key safety issues include the evidence-and lack thereof-for the effects of repeatedly inducing this altered mental state, and whether an adequate safety margin exists to rule out the neurotoxic effects seen in animal studies. This review includes evidence from multiple sources that raise substantial questions about both safety and effectiveness of ketamine and esketamine for psychiatric disorders.

Fixation vs Arthroplasty for Femoral Neck Fracture in Patients Aged 40-59 Years: A Propensity-Score-Matched Analysis.

Background: Internal fixation (IF) has historically been favored for the treatment of femoral neck fractures (FNFs) in young, nongeriatric patients. However, recent literature reporting high reoperation rates among those receiving IF, taken in conjunction with favorable survivorship of modern bearing surfaces in total hip arthroplasty (THA), has begun to question this paradigm. Our study sought to compare outcomes between IF and THA for FNFs in patients aged 40-59 years. Methods: Using the Truven MarketScan Database, we performed a retrospective propensity-score-matched cohort study on patients aged 40-59 years who underwent surgical management of an isolated FNF (THA or IF). Patients with pathologic fracture were not included. Analysis was conducted on patients aged 40-49 and 50-59 years separately. A subgroup analysis was performed on those patients with 1 year and 3 years of follow-up. Multivariate analysis, controlling for baseline patient information, was then performed. Results: Seven hundred sevety-eight 40- to 49-year-old patients and 3470 50- to 59-year-old matched patients (IF and THA) were included in this study. A multivariate analysis found that patients aged 40-49 years who underwent IF were at higher odds of both 1-year (odds ratio 2.35, 95% confidence interval 1.22-4.54, P = .011) and 3-year (odds ratio 5.68, 95% confidence interval 2.21-14.60, P < .001) reoperation. Similar results were found in those aged 50-59 years. While complication rates were similar, postoperative anemia and 90-day visits to the emergency room were more common after THA in both age cohorts. Conclusions: While THA is associated with increased postoperative anemia and resource utilization compared with IF, patients aged 40-59 years who undergo IF for FNF are at increased risk of reoperation in the first 3 postoperative years. This information should be used to assist in shared decision-making with patients in this age group.

Compartment syndrome of the upper extremity.

Compartment syndrome involves the sustained elevation of interstitial tissue pressures within an osteofascial envelope to nonphysiologic levels. Tissue injury involves a spectrum from reversible to irreversible damage and, therefore, early recognition and treatment is critical for optimal outcomes. This article reviews the nature of upper extremity compartment syndrome; considers the general classification scheme and potential causes; and discusses the pertinent anatomy, pathophysiology, treatment recommendations, and outcomes for this challenging condition.

Association of Pharmaceutical Industry Payments to Physicians With Prescription and Medicare Expenditures for Pimavanserin.

OBJECTIVE: This study aimed to quantify the association between pharmaceutical industry payments to physicians for pimavanserin and both pimavanserin prescription volume and Medicare expenditures. METHODS: This retrospective cross-sectional study used 2016 and 2017 data from Open Payments and the Medicare Part D Prescriber Public Use Files. The authors used Poisson regression models to quantify the association between physician payments for pimavanserin and pimavanserin prescription volume and linear regression models to quantify the association with Medicare expenditures for pimavanserin. RESULTS: Of 1,609 physicians who prescribed pimavanserin, 45% received payments, which totaled to $6,369,922. Each $10,000 in physician payments was associated with a 14% increase in pimavanserin prescription volume (incident rate ratio=1.14, 95% confidence interval [CI]=1.13-1.14). Every $100 in physician payments was associated with a $175.84 increase in Medicare pimavanserin expenditures (95% CI=$161.55-$190.13). CONCLUSIONS: Extensive physician payments have been associated with increased pimavanserin prescription volume and Medicare expenditures.