Rates of discontinuation and non-publication of upper and lower extremity fracture clinical trials.

PURPOSE: To our knowledge, no study has quantified the rate of discontinuation and nonpublication of randomized controlled trials (RCTs) regarding upper and lower extremity fractures. METHODS: We searched ClinicalTrials.gov on September 9th, 2020, for phase 3 and 4 RCTs pertaining to upper and lower extremity fractures. Trial completion status was determined using records available on ClinicalTrials.gov. Publication status was determined using records on ClinicalTrials.gov and by searching PubMed (MEDLINE), Embase, and Google Scholar. We queried corresponding authors on trial status if a peer-reviewed publication was not identified. RESULTS: Our final analysis included 142 RCTs, of which 57 (40.1%) were discontinued and 71 (50%) were unpublished. Thirty-six (of 57, 63.2%) discontinued trials failed to provide a reason for discontinuation, the most commonly identified reason for discontinuation was due to inadequate recruitment (13/21, 61.9%). Completed trials were more likely to reach publication (59/85; 69.4%; X2 = 32.92; P ≤ 0.001) than discontinued trials. Trials with more than 80 participants were less likely not to reach publication (AOR: 0.12; 95% CI 0.15-0.66). CONCLUSION: Our analysis of 142 upper and lower extremity fracture RCTs demonstrated one-half failed to reach publication and two-fifths were discontinued prior to trial completion. These findings indicate the need for increased guidance in developing, completing, and publishing RCTs in upper and lower extremity fractures. Discontinuation and nonpublication of orthopaedic RCTs hinder the public's access to collected data and negate the valued contribution from study participants. Discontinuation and non-publication of clinical trials may subject participants to potentially harmful interventions, limit the advancement of clinical research, and contribute to research waste. LEVEL OF EVIDENCE: III.

Assessment of Spin in the Abstracts of Systematic Reviews and Meta-analyses on Platelet-Rich Plasma Treatment in Orthopaedics: A Cross-sectional Analysis.

Background: Systematic reviews on the use of platelet-rich plasma (PRP) in orthopaedic surgery are abundant in current published literature. However, a beautification of results (referred to as spin) has been noted in abstracts across various aspects of medicine. Purpose: To determine the prevalence of spin in systematic reviews of PRP-related orthopaedic surgery abstracts. Study Design: Cross-sectional study. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Murad and Wang guidelines, we conducted a search in Medline, Embase, and the Cochrane Database for reviews on PRP-related orthopaedic surgery. The search included studies published from inception until June 30, 2021. Included were systematic reviews written in English that involved the use of PRP in the treatment of orthopaedic injuries in human participants. The abstracts of the included reviews were evaluated for the top 9 types of spin as described by Yavchitz et al in 2016. We determined the relationship between spin and study characteristics using odds ratios. Results: Of an initial 1560 studies, 176 were included. We found that 50 studies (28.4%) contained at least 1 form of spin. The 2 most common forms of spin found in our sample were type 5 ("Conclusion claims the beneficial effect of treatment despite high risk of bias"; n = 27 [15.3%]) and type 3 ("Selective reporting or overemphasis of efficacy in outcomes favoring beneficial effect of intervention"; n = 18 [10.2%]). No statistical significance was found between study characteristics and the presence of spin. Conclusion: Spin was present in 28% of the systematic reviews that covered PRP-related orthopaedic treatments. Spin was not associated with general study characteristics, including adherence to PRISMA guidelines or funding. Journals and authors should be aware of spin in articles and avoid its usage.

Increased Bite Distance From the Edge Lowers Risk of Pullout of Simple Sutures from Acellular Dermal Allograft.

PURPOSE: To investigate whether pullout strength in the acellular dermal allograft matrix (ADM) used for superior capsule reconstruction depends on the distance from the edge of the graft. METHODS: ADM used for superior capsule reconstruction was obtained and cut into 30 squares. Two sutures were placed through the center of each graft by using a loaded Keith needle and forming a simple stitch. The grafts were divided into 3 groups of 10 grafts with a distance of 5 mm, 10 mm or 15 mm from the closest edge of the graft, respectively. The grafts were then preloaded to 5 N and pulled to failure at a rate of 12 mm/s on an MTS 858 MiniBionix servohydraulic mechanical test frame. The load to failure was recorded as well as the stiffness of each graft. RESULTS: The mean load to failure was 34.5 N (SD 7.89) for the 5 mm grafts, 31.7 N (SD 5.99) for the 10 mm grafts, and 66.2 N (SD 18.4) for the 15 mm grafts. There was a significant difference (< 0.0001) between the large grafts (15 mm) and the 2 smaller grafts (10 mm, 5 mm). There was no significant difference in stiffness between the groups of graft (P 0.40). CONCLUSION: Placing the suture at least 15 mm from the edge of the graft increases the graft's ultimate yield strength to suture pullout. CLINICAL RELEVANCE: The depths of the suture in ADM could improve pullout strength for constructs of superior capsular reconstructions.

Thoracic dorsal arachnoid web with rapid onset of symptoms: A report of two cases and brief review of the literature.

BACKGROUND: Thoracic arachnoid webs are a rare entity and can be challenging to diagnose with sometimes subtle radiographic findings. Arachnoid webs can cause severe cord compression with associated syrinx and resulting myelopathy, weakness, sensory loss, and bowel/bladder dysfunction. There have been a little over 60 cases total reported in the literature with only one systematic review. The cases presented here have unique features including rapid onset of symptoms, symptomatic syrinx extending into the cervical spine, and intraoperative syrinx drainage, all of which are quite rare in the current published literature for arachnoid webs. CASE DESCRIPTION: Here, we present two patients, a 73-year-old man and 58-year-old man presenting with different symptoms and timing of symptom progression but both with "scalpel sign" and associated syrinx present on their MRIs. Each patient underwent a laminectomy with resection of arachnoid web with complete resolution of symptoms in the first case and significant improvement in the second case. Postoperative imaging in both cases showed almost complete resolution of the syrinx. CONCLUSION: Early clinical evaluation and workup followed by early surgical treatment can lead to dramatic improvement in outcomes after surgery. For patients that are symptomatic from an associated syrinx, a midline myelotomy to facilitate drainage can be considered to be done concomitantly with the arachnoid web resection.

Over 30% of Systematic Reviews and Meta-analyses Focused on Rotator Cuff Tear Treatments Contained Spin in the Abstract.

PURPOSE: The purpose of this study is to determine the prevalence of spin in the abstracts of systematic reviews and meta-analyses on treatments for rotator cuff tears and whether various study and publishing journal characteristics were associated with the presence of spin. METHODS: A search strategy was developed for Ovid MEDLINE and Ovid Embase to retrieve systematic reviews focused on treatments for rotator cuff tears. For an article to be included, it must meet the following criteria: (1) the article must be a systematic review with or without a meta-analysis, (2) the article must pertain to the treatment of rotator cuff tears, (3) the article must only contain human subjects, and (4) the article must be accessible in English. Systematic reviews were analyzed for spin using a previously developed classification scheme in a masked, duplicate manner. Binary logistic regression was used to examine independent associations via unadjusted odds ratios and 95% confidence intervals between the presence of spin and study characteristics. RESULTS: Search queries returned 932 articles, of which 121 systematic reviews and meta-analyses were eligible. A total of 36.4% (44/121) of systematic reviews contained spin. Among the general characteristics evaluated, there were no correlations with spin. CONCLUSIONS: Spin was present in more than one-third of systematic reviews and meta-analyses covering rotator cuff tear treatments. Spin was not associated with any general study or journal characteristics, which indicates that clinicians must be aware of the potential presence of spin in all such abstracts. CLINICAL RELEVANCE: Clinicians rely on systematic reviews and meta-analyses, especially abstracts of these articles, to provide succinct guidance on best practices in patient care. The presence of spin could adversely affect patient care; thus, steps should be taken to improve the reporting quality of abstracts on rotator cuff tear treatment.

An analysis of Google Trends following athletic injuries by high profile NBA players during the 2019 NBA finals.

CONTEXT: Injuries are common among high profile players in the National Basketball Association (NBA), and could provide an opportunity for physicians to provide accurate sports injury information and reliable rehabilitation data to the general public in the immediate aftermath. OBJECTIVES: To evaluate social media trends to investigate public interest in athletic injuries in the NBA and to evaluate the length of maintained interest in these injuries. METHODS: The Google Trends tool was used to analyze search data around two high profile players-Kevin Durant and Klay Thompson-who suffered injuries during the 2019 NBA Finals. The results were compared to the expected search forecast derived from an autoregressive integrated moving algorithm model. RESULTS: Both players were associated with a mean increase of 1,052.4% (standard deviation [SD], 703.96%) in relative search volumes for terms related to their injuries. This data showed a significant increase in search engine activity related to injuries associated with NBA players in the first 6.13 days (SD, 3.14 days) following the injuries, marking a substantial timeframe for public engagement. CONCLUSIONS: Search traffic information may be beneficial to the sports medicine community, as social media can provide a platform for patient education in a limited timeframe. By increasing patient awareness and knowledge regarding athletic injuries, social media can expand the pool of potential patients for physicians and surgeons.

Evaluation of 'spin' in the abstracts and articles of randomized controlled trials in pain literature and general anesthesia.

Aim: To evaluate the abstracts and articles of randomized controlled trials (RCTs) in pain literature and general anesthesia for the evidence of spin. Materials & methods: Following a priori protocol, we used a PubMed search for RCTs from a 2-year period. Data extracted using the Boutron spin definition for criteria. Results: A total of 163 articles were identified as RCTs with clear primary and secondary end points. A total of 33 trials were identified with nonsignificant primary end points. An 18/33 were found to have spin (54.5%). The spin was identified in the results, title and conclusion 12/18, 3/18 and 3/18, respectively. Conclusion: Spin was found in 54% of pain RCTs. With sensitive clinical concerns, such as chronic pain, any misrepresentation of validity could prove to have significant clinical consequences.

Public Online Interest in Injuries Sustained by National Football League Quarterbacks.

PURPOSE: To use Google search data to determine the public's interest in learning about athletic injuries sustained by NFL quarterbacks and to investigate how long this interest persists after the injuries. METHODS: We identified starting NFL quarterbacks during the 2019-2020 season online and used the official NFL injury report to determine whether an injury had occurred to a quarterback. We used the Google Trends tool to analyze search trends around a quarterback's injuries from July 22, 2019, to October 22, 2019. Google trends data was extracted as relative search volume over time. We then compared the results to the expected search forecast derived from an autoregressive integrated moving algorithm (ARIMA) model. RESULTS: All 6 injured quarterbacks were associated with increases (64% to 100%) in relative search volumes for terms related to their injury. Furthermore, the data showed a consistent increase in search engine activity around the injuries associated with NFL quarterbacks in the first 3 days, marking a particularly influential time frame for public engagement. CONCLUSION: Our data show an increase in Google traffic surrounding the injuries of prominent NFL quarterbacks within the first 3 days following their injuries. CLINICAL RELEVANCE: Social media can provide a platform for patient education through increasing patient awareness and knowledge regarding athletic injuries.

Retracing migration pattern in reproductive and non-reproductive female kutum Rutilus frisii, in south Caspian Sea, using otolith microchemistry.

Because trace elements of otoliths are considered a natural marker capable of recognizing the chemical composition of ambient water and fish migration history, these elements could be potentially used to analyse the movement of reproductive (R) and non-reproductive (NR) mature-sized fish. Supposedly, it is not essential for NR individuals to migrate to rivers for spawning because they do not have developed gonads. To investigate the potential differences in migration history between female R and NR kutum, Rutilus frisii, in the southwest waters of the Caspian Sea, the ratios of Sr, Ba, Mg, Na, K and P to Ca in otoliths (from the core to the edge) were examined using laser ablation-inductively coupled plasma-mass spectrometry. In NR fish, a significant increase in Sr:Ca ratio in the otoliths' growth rings, likely due to greater seawater residency, and an increase in Ba:Ca ratio in the last two rings were observed. Increased Ba:Ca ratio could be due to the movement of NR mature-sized fish to the coastal zones for foraging. Seasonal physiological factors such as gonad maturation and spawning activity are more likely to be involved in differences in the other elemental ratios (Mg, Na, K and P). These results suggest that microchemical analyses of growth rings of otolith can be used as a valuable tool for better understanding the movement pattern of different types of adult fish, which could be completed with data from other methods like tagging.

Evaluation of spin in the abstracts of systematic reviews and meta-analyses covering surgical management, or quality of life after surgical management, of osteoarthritis of the knee.

Objective: Our primary objective was to identify the prevalence of spin - misleading reporting practices that overemphasize benefit or underemphasize harm - within the abstracts of systematic reviews and meta-analyses focused on surgical management of osteoarthritis of the knee. Methods: A search string was developed to search Ovid MEDLINE and Ovid Embase for articles pertaining to surgical management, or quality of life after surgical management, of osteoarthritis of the knee. Titles and abstracts were screened according to our protocol, developed a priori, followed by full-text evaluation for spin in included articles. Study characteristics were simultaneously extracted with spin data and each included study received an AMSTAR-2 quality appraisal. All procedures were performed by two examiners in a masked, duplicate fashion. Results: Of the 1419 articles returned, 96 systematic reviews qualified for inclusion. 35.4% of the included abstracts (34/96) contained at least one type of spin with a total of 36 occurrences (two abstracts contained two types of spin). Selective reporting favoring benefit (type 3; 15/36, 41.7%) was the most prevalent followed by selective reporting of harms (type 6; 7/36, 19.4%). None of the abstracts contained spin types 2, 4, or 8. We found no significant association between spin and either AMSTAR-2 rating or extracted study characteristics. Conclusion: Of the included systematic reviews and meta-analyses, 35.4% contained spin in their abstract. To improve the reliability of systematic reviews and meta-analyses, researchers should act to minimize spin in future abstracts.

Measuring and Modeling Organochlorine Pesticide Response to Activated Carbon Amendment in Tidal Sediment Mesocosms.

Activated carbon (AC) sediment amendment for hydrophobic organic contaminants (HOCs) is attracting increasing regulatory and industrial interest. However, mechanistic and well-vetted models are needed. Here, we conduct an 18 month field mesocosm trial at a site containing dichlorodiphenyltrichloroethane (DDT) and chlordane. Different AC applications were applied and, for the first time, a recently published mass transfer model was field tested under varying experimental conditions. AC treatment was effective in reducing DDT and chlordane concentration in polyethylene (PE) samplers, and contaminant extractability by Arenicola brasiliensis digestive fluids. A substantial AC particle size effect was observed. For example, chlordane concentration in PE was reduced by 93% 6 months post-treatment in the powdered AC (PAC) mesocosm, compared with 71% in the granular AC (GAC) mesocosm. Extractability of sediment-associated DDT and chlordane by A. brasiliensis digestive fluids was reduced by at least a factor of 10 in all AC treatments. The model reproduced the relative effects of varying experimental conditions (particle size, dose, mixing time) on concentrations in polyethylene passive samplers well, in most cases within 25% of experimental observations. Although uncertainties such as the effect of long-term AC fouling by organic matter remain, the study findings support the use of the model to assess long-term implications of AC amendment.

Secondary environmental impacts of remedial alternatives for sediment contaminated with hydrophobic organic contaminants.

This study evaluates secondary environmental impacts of various remedial alternatives for sediment contaminated with hydrophobic organic contaminants using life cycle assessment (LCA). Three alternatives including two conventional methods, dredge-and-fill and capping, and an innovative sediment treatment technique, in-situ activated carbon (AC) amendment, are compared for secondary environmental impacts by a case study for a site at Hunters Point Shipyard, San Francisco, CA. The LCA results show that capping generates substantially smaller impacts than dredge-and-fill and in-situ amendment using coal-based virgin AC. The secondary impacts from in-situ AC amendment can be reduced effectively by using recycled or wood-based virgin AC as production of these materials causes much smaller impacts than coal-based virgin AC. The secondary environmental impacts are highly sensitive to the dredged amount and the distance to a disposal site for dredging, the capping thickness and the distance to the cap materials for capping, and the AC dose for in-situ AC amendment. Based on the analysis, this study identifies strategies to minimize secondary impacts caused by different remediation activities: optimize the dredged amount, the capping thickness, or the AC dose by extensive site assessments, obtain source materials from local sites, and use recycled or bio-based AC.

Cataracts.

Cataract surgery with an intraocular lens implant is one of the most common and thought to be the most effective surgical procedure in any field of medicine. Although aging is the most common cause, other factors are also known to be associated with cataract formation. Although cataracts are the domain of ophthalmology, primary care physicians are frequently the ones to whom patients present with vision complaints. Knowledge of cataract symptoms, how to evaluate them, and a basic understanding of the surgery to correct cataracts make primary care physicians an integral part of treating this leading cause of preventable blindness.

Modeling uptake of hydrophobic organic contaminants into polyethylene passive samplers.

Single-phase passive samplers are gaining acceptance as a method to measure hydrophobic organic contaminant (HOC) concentration in water. Although the relationship between the HOC concentration in water and passive sampler is linear at equilibrium, mass transfer models are needed for nonequilibrium conditions. We report measurements of organochlorine pesticide diffusion and partition coefficients with respect to polyethylene (PE), and present a Fickian approach to modeling HOC uptake by PE in aqueous systems. The model is an analytic solution to Fick's second law applied through an aqueous diffusive boundary layer and a polyethylene layer. Comparisons of the model with existing methods indicate agreement at appropriate boundary conditions. Laboratory release experiments on the organochlorine pesticides DDT, DDE, DDD, and chlordane in well-mixed slurries support the model's applicability to aqueous systems. In general, the advantage of the model is its application in the cases of well-agitated systems, low values of polyethylene-water partioning coefficients, thick polyethylene relative to the boundary layer thickness, and/or short exposure times. Another significant advantage is the ability to estimate, or at least bound, the needed exposure time to reach a desired CPE without empirical model inputs. A further finding of this work is that polyethylene diffusivity does not vary by transport direction through the sampler thickness.

Effects of Eyjafjallajökull volcanic ash on innate immune system responses and bacterial growth in vitro.

BACKGROUND: On 20 March 2010, the Icelandic volcano Eyjafjallajökull erupted for the first time in 190 years. Despite many epidemiological reports showing effects of volcanic ash on the respiratory system, there are limited data evaluating cellular mechanisms involved in the response to ash. Epidemiological studies have observed an increase in respiratory infections in subjects and populations exposed to volcanic eruptions. METHODS: We physicochemically characterized volcanic ash, finding various sizes of particles, as well as the presence of several transition metals, including iron. We examined the effect of Eyjafjallajökull ash on primary rat alveolar epithelial cells and human airway epithelial cells (20-100 µg/cm(2)), primary rat and human alveolar macrophages (5-20 µg/cm(2)), and Pseudomonas aeruginosa (PAO1) growth (3 µg/104 bacteria). RESULTS: Volcanic ash had minimal effect on alveolar and airway epithelial cell integrity. In alveolar macrophages, volcanic ash disrupted pathogen-killing and inflammatory responses. In in vitro bacterial growth models, volcanic ash increased bacterial replication and decreased bacterial killing by antimicrobial peptides. CONCLUSIONS: These results provide potential biological plausibility for epidemiological data that show an association between air pollution exposure and the development of respiratory infections. These data suggest that volcanic ash exposure, while not seriously compromising lung cell function, may be able to impair innate immunity responses in exposed individuals.

Discovery of benzylisothioureas as potent divalent metal transporter 1 (DMT1) inhibitors.

Inhibition of intestinal brush border DMT1 offers a novel therapeutic approach to the prevention and treatment of disorders of iron overload. Several series of diaryl and tricyclic benzylisothiourea compounds as novel and potent DMT1 inhibitors were discovered from the original hit compound 1. These compounds demonstrated in vitro potency against DMT1, desirable cell permeability properties and a dose-dependent inhibition of iron uptake in an acute rat model of iron hyperabsorption. Tricyclic compounds increased the in vitro potency by up to 16-fold versus the original hit. Diaryl compounds 6b and 14a demonstrated significant iron absorption inhibition in vivo with both 25 and 50 mg/kg doses. The diaryl and tricyclic compounds described in this report represent promising structural templates for further optimization.

Synthesis and biological evaluation of substituted pyrazoles as blockers of divalent metal transporter 1 (DMT1).

Three distinct series of substituted pyrazole blockers of divalent metal transporter 1 (DMT1) were elaborated from the high-throughput screening pyrazolone hit 1. Preliminary hit-to-lead efforts revealed a preference for electron-withdrawing substituents in the 4-amido-5-hydroxypyrazole series 6a-l. In turn, this preference was more pronounced in a series of 4-aryl-5-hydroxypyrazoles 8a-j. The representative analogs 6f and 12f were found to be efficacious in a rodent model of acute iron hyperabsorption. These three series represent promising starting points for lead optimization efforts aimed at the discovery of DMT1 blockers as iron overload therapeutics.

Remediation of alachlor and atrazine contaminated water with zero-valent iron nanoparticles.

Zero-valent iron nanoparticles (nZVI, diameter < 90 nm, specific surface area = 25 m(2) g(-1)) have been used under anoxic conditions for the remediation of pesticides alachlor and atrazine in water. While alachlor (10, 20, 40 mg L(-1)) was reduced by 92-96% within 72 h, no degradation of atrazine was observed. The alachlor degradation reaction was found to obey first-order kinetics very closely. The reaction rate (35.5 x 10(-3)-43.0 x 10(-3) h(-1)) increased with increasing alachlor concentration. The results are in conformity with other researchers who worked on these pesticides but mostly with micro ZVI and iron filings. This is for the first time that alachlor has been degraded under reductive environment using nZVI. The authors contend that nZVI may prove to be a simple method for on-site treatment of high concentration pesticide rinse water (100 mg L(-1)) and for use in flooring materials in pesticide filling and storage stations.