A Cost-Effectiveness Analysis of the Various Treatment Options for Distal Radius Fractures.

Purpose: To conduct a cost-effectiveness study of nonsurgical and surgical treatment options for distal radius fractures using distinct posttreatment outcome patterns. Methods: We created a decision tree to model the following treatment modalities for distal radius fractures: nonsurgical management, external fixation, percutaneous pinning, and plate fixation. Each node of the model was associated with specific costs in dollars, a utility adjustment (quality-adjusted life year [QALY]), and a percent likelihood. The nodes of the decision tree included uneventful healing, eventful healing and no further intervention, carpal tunnel syndrome, trigger finger, and tendon rupture as well as associated treatments for each event. The percent probabilities of each transition state, QALY values, and costs of intervention were gleaned from a systematic review. Rollback and incremental cost-effectiveness ratio analyses were conducted to identify optimal treatment strategies. Threshold values of $50,000/QALY and $100,000/QALY were used to distinguish the modalities in the incremental cost-effectiveness ratio analysis. Results: Both the rollback analysis and the incremental cost-effectiveness ratio analysis revealed nonsurgical management as the predominant strategy when compared with the other operative modalities. Nonsurgical management dominated external fixation and plate fixation, although it was comparable with percutaneous fixation, yielding a $2,242 lesser cost and 0.017 lesser effectiveness. Conclusions: The cost effectiveness of nonsurgical management is driven by its decreased cost to the health care system. Plate and external fixation have been shown to be both more expensive and less effective than other proposed treatments. Percutaneous pinning has demonstrated more favorable effectiveness in the literature than plate and external fixation and, thus, may be more cost effective in certain circumstances. Future studies may find value in investigating further clinical aspects of distal radius fractures and their association with nonsurgical management versus that with plate fixation. Type of study/level of evidence: Economic/decision analysis II.

A thermosensitive PCNA allele underlies an ataxia-telangiectasia-like disorder.

Proliferating cell nuclear antigen (PCNA) is a sliding clamp protein that coordinates DNA replication with various DNA maintenance events that are critical for human health. Recently, a hypomorphic homozygous serine to isoleucine (S228I) substitution in PCNA was described to underlie a rare DNA repair disorder known as PCNA-associated DNA repair disorder (PARD). PARD symptoms range from UV sensitivity, neurodegeneration, telangiectasia, and premature aging. We, and others, previously showed that the S228I variant changes the protein-binding pocket of PCNA to a conformation that impairs interactions with specific partners. Here, we report a second PCNA substitution (C148S) that also causes PARD. Unlike PCNA-S228I, PCNA-C148S has WT-like structure and affinity toward partners. In contrast, both disease-associated variants possess a thermostability defect. Furthermore, patient-derived cells homozygous for the C148S allele exhibit low levels of chromatin-bound PCNA and display temperature-dependent phenotypes. The stability defect of both PARD variants indicates that PCNA levels are likely an important driver of PARD disease. These results significantly advance our understanding of PARD and will likely stimulate additional work focused on clinical, diagnostic, and therapeutic aspects of this severe disease.

Impact of Patellar Tendinopathy on Player Performance in the National Basketball Association.

BACKGROUND: The extent to which patellar tendinopathy affects National Basketball Association (NBA) athletes has not been thoroughly elucidated. PURPOSE: To assess the impact patellar tendinopathy has on workload, player performance, and career longevity in NBA athletes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: NBA players diagnosed with patellar tendinopathy between the 2000-2001 and 2018-2019 seasons were identified through publicly available data. Characteristics, return to play (RTP), player statistics, and workload data were compiled. The season of diagnosis was set as the index year, and the statistical analysis compared post- versus preindex data acutely and in the long term, both within the injured cohort and with a matched healthy NBA control cohort. RESULTS: A total of 46 NBA athletes were included in the tendinopathy group; all 46 players returned to the NBA after their diagnosis. Compared with controls, the tendinopathy cohort had longer careers (10.50 ± 4.32 vs 7.18 ± 5.28 seasons; P < .001) and played more seasons after return from injury (4.26 ± 2.46 vs 2.58 ± 3.07 seasons; P = .001). Risk factors for patellar tendinopathy included increased workload before injury (games started, 45.83 ± 28.67 vs 25.01 ± 29.77; P < .001) and time played during the season (1951.21 ± 702.09 vs 1153.54 ± 851.05 minutes; P < .001) and during games (28.71 ± 6.81 vs 19.88 ± 9.36 minutes per game; P < .001). Players with increased productivity as measured by player efficiency rating (PER) were more likely to develop patellar tendinopathy compared with healthy controls (15.65 ± 4.30 vs 12.76 ± 5.27; P = .003). When comparing metrics from 1 year preinjury, there was a decrease in games started at 1 year postinjury (-12.42 ± 32.38 starts; P = .028) and total time played (-461.53 ± 751.42 minutes; P = .001); however, PER at 1 and 3 years after injury was unaffected compared with corresponding preinjury statistics. CONCLUSION: NBA players with a higher PER and significantly more playing time were more likely to be diagnosed with patellar tendinopathy. Player performance was not affected by the diagnosis of patellar tendinopathy, and athletes were able to RTP without any impact on career longevity.

Concussion in National Football League Athletes Is Not Associated With Increased Risk of Acute, Noncontact Lower Extremity Musculoskeletal Injury.

BACKGROUND: Impaired neuromuscular function after concussion has recently been linked to increased risk of lower extremity injuries in athletes. PURPOSE: To determine if National Football League (NFL) athletes have an increased risk of sustaining an acute, noncontact lower extremity injury in the 90-day period after return to play (RTP) and whether on-field performance differs pre- and postconcussion. STUDY DESIGN: Cohort study, Level of evidence, 3. METHODS: NFL concussions in offensive players from the 2012-2013 to the 2016-2017 seasons were studied. Age, position, injury location/type, RTP, and athlete factors were noted. A 90-day RTP postconcussive period was analyzed for lower extremity injuries. Concussion and injury data were obtained from publicly available sources. Nonconcussed, offensive skill position NFL athletes from the same period were used as a control cohort, with the 2014 season as the reference season. Power rating performance metrics were calculated for ±1, ±2, and ±3 seasons pre- and postconcussion. Conditional logistic regression was used to determine associations between concussion and lower extremity injury as well as the relationship of concussions to on-field performance. RESULTS: In total, 116 concussions were recorded in 108 NFL athletes during the study period. There was no statistically significant difference in the incidence of an acute, noncontact lower extremity injury between concussed and control athletes (8.5% vs 12.8%; P = .143), which correlates with an odds ratio of 0.573 (95% CI, 0.270-1.217). Days (66.4 ± 81.9 days vs 45.1 ± 69.2 days; P = .423) and games missed (3.67 ± 3.0 vs 2.9 ± 2.7 games; P = .470) were similar in concussed athletes and control athletes after a lower extremity injury. No significant changes in power ratings were noted in concussed athletes in the acute period (±1 season to injury) when comparing pre- and postconcussion. CONCLUSION: Concussed, NFL offensive athletes did not demonstrate increased odds of acute, noncontact, lower extremity injury in a 90-day RTP period when compared with nonconcussed controls. Immediate on-field performance of skill position players did not appear to be affected by concussion.

Concussion Is Associated With Increased Odds of Acute Lower-Extremity Musculoskeletal Injury Among National Basketball Association Players.

PURPOSE: To determine the odds of sustaining an acute lower-extremity (LE) musculoskeletal injury during the 90-day period after return-to-play (RTP) from concussion in National Basketball Association (NBA) athletes. METHODS: Concussion data for NBA players were collected from the 1999-2000 to 2017-2018 seasons, from publicly available sources. Age, position, injury, time to RTP, and demographic factors were collected. The 90-day period after each case of concussion was reviewed for acute noncontact LE musculoskeletal injury. Control athletes without a documented history of concussion were matched to concussed athletes by age, body mass index, position, and experience. Conditional logistic regression with a calculated odds ratio and a 95% confidence interval were used to assess the association between concussion and subsequent risk of LE injury. RESULTS: In total, 189 concussions were documented in 153 athletes. Of these, 140 cases were the first recorded instance of concussion in players with publicly available data. Thirty-six (25.7%) athletes sustained a LE injury within 90 days of concussion; 26 (20.2%) were non-season-ending and included in RTP analysis. The odds of sustaining an acute LE musculoskeletal injury within the 90-day period after concussion was 4.69 times greater in concussed players compared with controls (95% confidence interval 1.96-11.23, P < .001). There was no significant difference in games (4.2 ± 5.0 vs 4.7 ± 4.7 games, P = .566) or days (18.5 ± 39.1 days vs 10.9 ± 10.6 days, P = .912) missed between concussed players with LE injury and nonconcussed controls. The most common LE injuries in concussed athletes were ligament sprains/tears (65%). CONCLUSIONS: Concussed NBA athletes have increased odds for sustaining an acute LE musculoskeletal injury within 90 days of RTP compared with nonconcussed controls. The most common injuries were ligament strains or tears. Changes in neuromotor control and proprioception following a concussion should be evaluated in high-level basketball players returning to sport. LEVEL OF EVIDENCE: Level III, Case-Control Study.

Preoperative Patient-Centric Predictors of Postoperative Outcomes in Patients Undergoing Arthroscopic Meniscectomy.

PURPOSE: To determine the minimal clinically important difference (MCID) using Patient-Reported Outcome Measurement Information System (PROMIS) computer-adaptive testing assessments in patients undergoing arthroscopic partial meniscectomy. The secondary purpose was to identify which preoperative patient factors are associated with MCID achievement. METHODS: Three PROMIS computer-adaptive testing assessments (Physical Function [PF], Pain Interference [PI], and Depression [D]) were administered to all patients presenting to 1 of 2 board-certified, sports medicine orthopaedic surgeons. Patients with Current Procedural Terminology codes of 29880 or 29881 were chart reviewed for a host clinical and demographic factors. PROMIS scores were assessed for improvement and patient characteristics were assessed for influence on any improvement. MCID was calculated according to the distribution methodology and receiver operating characteristics were used to assess preoperative scores predictive ability. RESULTS: In total, 166 patients met inclusion criteria (58 exclusions). Postoperative PROMIS-PF (45.6), PROMIS-PI (54.6), and PROMIS-D (44.1) significantly improved at least 3 months after surgery when compared with baseline (P = .002). MCID values for PROMIS-PF, PROMIS-PI, and PROMIS-D were 3.5, 3.3, and 4.4, respectively. Individuals with PROMIS-PF scores below 34.9 yielded an 82% probability of achieving MCID, while PROMIS-PI scores above 67.5 yielded an 86% probability of achieving MCID and a cutoff of 58.9 for PROMIS-D yielded a 60% probability of achieving MCID, with 90% specificity. CONCLUSIONS: PROMIS scores, obtained preoperatively, were shown to be valid predictors of postoperative clinical improvement in patients undergoing meniscectomy. Our findings suggest that patients with physical function scores of 34.9 or less have an increased probability of reaching a minimal clinically important difference. Similarly, patients with pain interference scores of 67.5 and above have increased probability of reaching MCID for pain interference. These cutoffs may be used by physicians to aid in the counseling of patients considering arthroscopic meniscectomy. LEVEL OF EVIDENCE: IV, Case Series.

Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation.

Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIß, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulatory segment, a variable linker region, and a hub domain, which is responsible for oligomerization. The four proteins differ primarily in linker length and composition because of extensive alternative splicing. Here, we report the heterogeneity of CaMKII transcripts in three complex samples of human hippocampus using deep sequencing. We showed that hippocampal cells contain a diverse collection of over 70 CaMKII transcripts from all four CaMKII-encoding genes. We characterized the Ca2+/CaM sensitivity of hippocampal CaMKII variants spanning a broad range of linker lengths and compositions. The effect of the variable linker on Ca2+/CaM sensitivity depended on the kinase and hub domains. Moreover, we revealed a previously uncharacterized role for the hub domain as an allosteric regulator of kinase activity, which may provide a pharmacological target for modulating CaMKII activity. Using small-angle x-ray scattering and single-particle cryo-electron microscopy (cryo-EM), we present evidence for extensive interactions between the kinase and the hub domains, even in the presence of a 30-residue linker. Together, these data suggest that Ca2+/CaM sensitivity in CaMKII is homolog dependent and includes substantial contributions from the hub domain. Our sequencing approach, combined with biochemistry, provides insights into understanding the complex pool of endogenous CaMKII splice variants.