Colorectal Cancer Diagnosis through Breath Test Using a Portable Breath Analyzer-Preliminary Data.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis.

The discovery of genetic causes of inherited skin disorders has been pivotal to the understanding of epidermal differentiation, function, and renewal. Here we show via exome sequencing that mutations in ASPRV1 (aspartic peptidase retroviral-like 1) cause a dominant Mendelian disorder featuring palmoplantar keratoderma and lamellar ichthyosis, a phenotype that has otherwise been exclusively recessive. ASPRV1 encodes a mammalian-specific and stratified epithelia-specific protease important in processing of filaggrin, a critical component of the uppermost epidermal layer. Three different heterozygous ASPRV1 missense mutations in four unrelated ichthyosis kindreds segregate with disease and disrupt protein residues within close proximity to each other and autocatalytic cleavage sites. Expression of mutant ASPRV1 proteins demonstrates that all three mutations alter ASPRV1 auto-cleavage and filaggrin processing, a function vital to epidermal barrier integrity.

The Potential Effect of Lowering the Threshold of Statistical Significance From P < .05 to P < .005 in Orthopaedic Sports Medicine.

PURPOSE: To determine how changing the P value threshold of statistical significance from .05 to .005 could affect the statistical significance of findings in previously published orthopaedic sports medicine randomized controlled trials (RCTs). METHODS: The authors searched PubMed from January 1, 2016, to December 31, 2017, for RCTs published in the American Journal of Sports Medicine, Arthroscopy, and Knee Surgery, Sports Traumatology, Arthroscopy. Data were extracted blinded and in duplicate fashion by 2 of us. The authors then extracted P value data for primary end points, since RCTs are most often powered for these end points. Discrepancies were resolved by consensus. Google Forms were used for data extraction and STATA 15.1 for the data analysis. RESULTS: In total, 275 primary end points were identified from 132 trials. Analysis of primary end points found 45.8% (126/275) had a P value less than .05 and were classified as statistically significant under the current threshold, whereas 54.2% (149/275) had a P value greater than .05 and were not classified as suggestive. Of those end points that were previously considered statistically significant, 38.9% (49/126) were less than .005, whereas 61.1% (77/126) were between .005 and .05 and thereby would be reclassified as suggestive rather than statistically significant under the proposed threshold. Overall, when analyzing the 275 primary end points, we found only 49 (17.8%) of the end points were less than .005 and would hold statistical significance with the proposed threshold. CONCLUSIONS: The results suggest that if the threshold of statistical significance were to change to .005, the significance of orthopaedic sports medicine RCTs would be heavily altered. The authors also acknowledge the many issues research faces in regard to P value reliability and therefore interpretation of study results. Because P values from RCTs can often influence the ways physicians choose interventions, it is important to implement methodology that decreases incidence of bias and misrepresentation of these results. However, the authors also understand that lowering the P value could increase the needed sample size and by consequence increase study costs as well, while not directly correlating to clinical significance. Thus, the authors recommend that this proposed threshold should be further evaluated and cautiously interpreted. CLINICAL RELEVANCE: If the statistical significance threshold is changed, clinical practice guideline recommendations also may be affected.

Preictal variability of high-frequency oscillation rates in refractory epilepsy.

OBJECTIVE: High-frequency oscillations (HFOs) have shown promising utility in the spatial localization of the seizure onset zone for patients with focal refractory epilepsy. Comparatively few studies have addressed potential temporal variations in HFOs, or their role in the preictal period. Here, we introduce a novel evaluation of the instantaneous HFO rate through interictal and peri-ictal epochs to assess their usefulness in identifying imminent seizure onset. METHODS: Utilizing an automated HFO detector, we analyzed intracranial electroencephalographic data from 30 patients with refractory epilepsy undergoing long-term presurgical evaluation. We evaluated HFO rates both as a 30-minute average and as a continuous function of time and used nonparametric statistical methods to compare individual and population-level differences in rate during peri-ictal and interictal periods. RESULTS: Mean HFO rate was significantly higher for all epochs in seizure onset zone channels versus other channels. Across the 30 patients of our cohort, we found no statistically significant differences in mean HFO rate during preictal and interictal epochs. For continuous HFO rates in seizure onset zone channels, however, we found significant population-wide increases in preictal trends relative to interictal periods. Using a data-driven analysis, we identified a subset of 11 patients in whom either preictal HFO rates or their continuous trends were significantly increased relative to those of interictal baseline and the rest of the population. SIGNIFICANCE: These results corroborate existing findings that HFO rates within epileptic tissue are higher during interictal periods. We show this finding is also present in preictal, ictal, and postictal data, and identify a novel biomarker of preictal state: an upward trend in HFO rate leading into seizures in some patients. Overall, our findings provide preliminary evidence that HFOs can function as a temporal biomarker of seizure onset.

"Knee osteoarthritis and current research for evidence-are we on the right way?"

PURPOSE: An estimated 85% of research is of limited value or wasted because the wrong research questions are addressed. We sought to identify research gaps using American Academy of Orthopaedic Surgeon (AAOS) clinical practice guidelines Treatment of Osteoarthritis of the Knee and Surgical Management of Osteoarthritis of the Knee. Using these recommendations, we conducted searches of ClinicalTrials.gov to discover the extent to which new and ongoing research addresses areas of deficiency. METHODS: For each recommendation in the AAOS guidelines, we created participants, intervention, comparator, outcomes questions, and search strings using a systematic process. Searches were then conducted of ClinicalTrials.gov to locate relevant studies. RESULTS: Our searches of ClinicalTrials.gov returned 945 studies for surgical and 1416 for non-surgical management of osteoarthritis. Of the 945 studies returned using our search string for surgical trials, 186 (20%) were relevant to 30 (79%) of the 38 recommendations made within the surgical management guideline. Of the 1416 studies returned using our search for non-surgical trials, 360 (25%) were relevant to 16 (89%) of the 18 recommendations made within the conservative management guideline. CONCLUSIONS: The development of clinical practice guidelines is a unique opportunity to simultaneously redefine day-to-day decision-making and provide a critical analysis of the status of the literature. Upon our search of the literature since the guidelines introduction, we have found that some inconclusive areas have received more attention than others. Our results should guide researchers towards conducting research on the topics most in need and, by doing so, strengthen the clinical practice guideline recommendations.

Variable methodological quality and use found in systematic reviews referenced in STEMI clinical practice guidelines.

BACKGROUND: The objective of this study was to assess the methodological quality and clarity of reporting of the systematic reviews (SRs) supporting clinical practice guideline (CPG) recommendations in the management of ST-elevation myocardial infarction (STEMI) across international CPGs. METHODS: We searched 13 guideline clearinghouses including the National Guideline Clearinghouse and Guidelines International Network (GIN). To meet inclusion criteria CPGs must be pertinent to the management of STEMI, endorsed by a governing body or national organization, and written in English. We retrieved SRs from the reference sections using a combination of keywords and hand searching. Two investigators scored eligible SRs using AMSTAR and PRISMA. RESULTS: We included four CPGs. We extracted 71 unique SRs. These SRs received AMSTAR scores ranging from 1 (low) to 9 (high) on an 11-point scale. All CPGs consistently underperformed in areas including disclosure of funding sources, risk of bias, and publication bias according to AMSTAR. PRISMA checklist completeness ranged from 44% to 96%. The PRISMA scores indicated that SRs did not provide a full search strategy, study protocol and registration, assessment of publication bias or report funding sources. Only one SR was referenced in all four CPGs. All CPGs omitted a large subset of available SRs cited by other guidelines. CONCLUSIONS: Our study demonstrates the variable quality of SRs used to establish recommendations within guidelines included in our sample. Although guideline developers have acknowledged this variability, it remains a significant finding that needs to be addressed further. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Publication Rates in Podium and Poster Presentations at the 2012-2014 American Association of Hip and Knee Surgeons Annual Meetings.

BACKGROUND: Subspecialty conferences are an important forum for disseminating the latest research relevant to clinical practice. The purpose of this study was to identify publication rates in podium and poster abstracts for the American Association of Hip and Knee Surgeons (AAHKS) Annual Meeting and to identify the most common journals of publication and the reasons for nonpublication. METHODS: Six hundred ten accepted abstracts (182 podium presentations, 428 posters) from the 2012-2014 AAHKS meetings were searched using Google, Google Scholar, and PubMed. If an abstract could not be found after efforts by multiple searchers, the first author was emailed to determine where the research was published or why it was not published. For articles that were published, the journal, time to publication, and journal impact factor were noted. RESULTS: The overall rate of publication was 71% (436/610). Podium presentations (164/182, 90%) were published at a higher rate than posters (271/428, 63%). The most common journal of publication was the Journal of Arthroplasty (218/436, 50%), followed by Clinical Orthopaedics and Related Research (77/436, 18%) and The Journal of Bone and Joint Surgery (40/436, 9%). Average time to publication was 14.5 months (range, -4 to 44 months) from the date of the conference in which it was presented. CONCLUSION: Presentations at the AAHKS annual meeting have an impressive rate of publication. The research presented at the meeting is impactful and high quality, warranting consideration for future publication.

Walking the Labyrinth: Considering Mental Health Consumer Experience, Meaning Making, and the Illumination of the Sacred in a Forensic Mental Health Setting.

The purpose of this study is to explore the unique meaning and experience associated with walking a unicursal seven circuit outdoor Chartress Labyrinth and 11 circuit indoor Chartress Labyrinth for persons residing at a forensic mental health care facility. Over the past several decades labyrinths have enjoyed something of a renaissance and are often utilized by spiritual care practitioners and health care clinicians in order to support reflection, stress reduction, and the exploration of personal wellness in a sacred setting. Labyrinths are used in many settings including places of worship, hospitals, long-term care facilities, and parks. While labyrinths are becoming more prevalent, an understanding of their impact, particularly in the mental health context, is limited. This qualitative study supports a novel investigation of the meaning associated with participation in walking a labyrinth for persons residing at a forensic mental health care facility. The study design is a qualitative methodology involving transcribed interviews with 12 individuals resident at the Southwest Centre for Forensic Mental Health Care who participated in the 'Walking the Labyrinth' program as facilitated by spiritual care staff. A standardized interview protocol was utilized and the collected data was coded for themes. Several methods were employed to establish trustworthiness including triangulation by analyst and by theory/perspective. Member checking was also utilized in order to further validate the themes. Recommendations related to potential health care applications for labyrinths are identified. These include a focus upon the linkage between mental health care planning and labyrinth participation.

Network meta-analysis: What is its purpose in Orthopaedic literature?

Systematic reviews, of level-I primary literature, are the gold standard for the formation of Clinical Practice Guidelines in Orthopaedic Surgery. When systematic reviews have multiple groups of data, meta-analyses can be conducted to analyse the direct comparison of the data points (pairwise meta-analysis). Over recent years, statisticians have created a new statistical model called network meta-analyses that can be applied to systematic reviews. network meta-analyses allow for comparison of different treatment outcomes that may or may not have been directly assessed through level-I primary studies. network meta-analyses are appearing more and more in Orthopaedic Surgery literature; therefore, in this article, we discuss what a Network Meta-analysis is and its application in Orthopaedics.

Analysis of the Evidence Underpinning the American Academy of Orthopedic Surgeons Knee Osteoarthritis Clinical Practice Guidelines.

CONTEXT: Clinical practice guidelines (CPGs) are vital to establishing a standardized and evidence-based approach in medicine. These guidelines rely on the use of methodologically sound clinical trials, and the subsequent reporting of their methodology. OBJECTIVE: To evaluate the completeness of randomized controlled trials (RCTs) underpinning CPGs published by the American Academy of Orthopedic Surgeons (AAOS) for management of osteoarthritis of the knee. DATA SOURCES: We searched the most recent AAOS CPGs for surgical and nonsurgical management of osteoarthritis of the knee for RCTs. To estimate the necessary sample size, we performed a power analysis using OpenEpi 3.0 (openepi.com). STUDY SELECTION: Two authors independently screened the reference sections of the included CPGs. Included studies met the definition of an RCT, were retrievable in the English language, and were cited in at least one of the included CPGs. STUDY DESIGN: Meta-Analysis. LEVEL OF EVIDENCE: Level 1a. DATA EXTRACTION: We performed double-blind screening and extraction of RCTs included in the AAOS CPGs. We evaluated each RCT for adherence to the Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist. A multiple regression analysis was conducted to assess CONSORT adherence against characteristics of included studies (ie, type of intervention, funding source, etc). RESULTS: Our study included 179 RCTs. The overall adherence was 68.5% with significant differences between those published before and since the development of the 2010 CONSORT guidelines (P = 0.02). We found that RCTs receiving funding from industry/private sources as well as studies that included a conflict of interest statement showed more completeness than RCTs that reported receiving no funding (P < 0.01). CONCLUSION: We found suboptimal CONSORT adherence for RCTs cited in AAOS CGPs for management of osteoarthritis of the knee. Therefore, the CPGs are likely supported by outdated evidence and lack of high-quality reporting. It is important that evidence used to guide clinical decision making be of the highest quality in order to optimize patient outcomes. In order for clinicians to confer the greatest benefits to their patients, CPGs should provide the totality of evidence and emphasize emerging high-quality RCTs to ensure up-to-date, evidence-based clinical decision-making.

The presence of person-centered language in orthopedic-related amputation research: a cross-sectional analysis.

CONTEXT: Amputations are routine in orthopedics, specifically during trauma and when patients have recurrent surgical site infections. When undergoing amputations, patients must combat the psychosocial factors associated with the loss of an extremity, including stigmatization. OBJECTIVES: This study analyzes the presence of person-centered language (PCL) within amputation-related orthopedic publications in the top orthopedic journals. METHODS: We conducted a cross-sectional analysis with a database search on February 14, 2021 utilizing PubMed. Utilizing a previously published search string, we isolated studies that were published in the top 20 orthopedic journals based on the Google h5-index. In addition to the top 20 orthopedic journals, we included the top two hand and foot & ankle journals in our search to incorporate more amputation literature. Our search yielded 687 returns. The sample was then randomized, and the first 300 studies that fit our inclusion criteria were examined for prespecified non-PCL terminology. RESULTS: Our results show that 157 (52.2%) studies were adherent to PCL according to the American Medical Association's Manual of Style 10th Edition (AMAMS). Of the 143 (47.7%) studies that were not adherent to PCL, 51 studies (35.7%) had more than one type of non-PCL language. The term "amputee," which is being labeled as identity-first language (IFL), was found in 101 articles (33.7%). Further investigation found that 73.3% (74/101) of the studies containing IFL were found to have other non-PCL terms. Of the other studies in the sample, non-PCL was found 34.7% (88/199) of the time. This analysis was done due to the discrepancies in stigmatization of the term "amputee." No statistical association was found between adherence to PCL and study characteristics. CONCLUSIONS: Our findings show that amputation literature within the top orthopedic journals has limited adherence to PCL. Additionally, the use of the term "amputee," which is widely accepted by the amputation community, resulted in a greater rate of non-PCL terminology within orthopedic amputation literature. Efforts should be implemented within orthopedics to avoid the use of stigmatizing language, regarding individuals that underwent amputations, to minimize psychosocial stressors.

Insights Into Patients Questions Over Bunion Treatments: A Google Study.

Background: Approximately 1 in 4 adults will develop hallux valgus (HV). Up to 80% of adult Internet users reference online sources for health-related information. Overall, with the high prevalence of HV combined with the numerous treatment options, we believe patients are likely turning to Internet search engines for questions relevant to HV. Using Google's people also ask (PAA) or frequently asked questions (FAQs) feature, we sought to classify these questions, categorize the sources, as well as assess their levels of quality and transparency. Methods: On October 9, 2022, we searched Google using these 4 phrases: "hallux valgus treatment," "hallux valgus surgery," "bunion treatment," and "bunion surgery." The FAQs were classified in accordance with the Rothwell Classification schema and each source was categorized. Lastly, transparency and quality of the sources' information were evaluated with the Journal of the American Medical Association's (JAMA) Benchmark tool and Brief DISCERN, respectively. Results: Once duplicates and FAQs unrelated to HV were removed, our search returned 299 unique FAQs. The most common question in our sample was related to the evaluation of treatment options (79/299, 26.4%). The most common source type was medical practices (158/299, 52.8%). Nearly two-thirds of the answer sources (184/299; 61.5%) were lacking in transparency. One-way analysis of variance revealed a significant difference in mean Brief DISCERN scores among the 5 source types, F(4) = 54.49 (P < .001), with medical practices averaging the worst score (12.1/30). Conclusion: Patients seeking online information concerning treatment options for HV search for questions pertaining to the evaluation of treatment options. The source type encountered most by patients is medical practices; these were found to have both poor transparency and poor quality. Publishing basic information such as the date of publication, authors or reviewers, and references would greatly improve the transparency and quality of online information regarding HV treatment. Level of Evidence: Level V, mechanism-based reasoning.

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.

Cemented vs Uncemented hemiarthroplasties for femoral neck fractures: An overlapping systematic review and evidence appraisal.

BACKGROUND: The purpose of our study is to assess the methodology of overlapping systematic reviews related to cemented vs uncemented hip hemiarthroplasties for the treatment of femoral neck fractures to find the study with the best evidence. Also, we assess the gaps in methodology and information to help with direction of future studies. METHODS: A systematic search was conducted in September 2022 using Pubmed, Embase, and Cochrane Library. Clinical outcome data and characteristics of each study were extracted to see which treatment had better favorability. The outcomes and characteristics extracted from each study includes, first author, search date, publication journal and date, number of studies included, databases, level of evidence, software used, subgroup analyses that were conducted, and heterogeneity with the use of I2 statistics Methodological quality information was extracted from each study using four different methodologic scores (Oxford Levels of Evidence; Assessment of Multiple Systematic Reviews (AMSTAR); Quality of reporting of meta-analyses (QUROM); Oxman and Guyatt. After that, the Jadad decision algorithm was used to identify which studies in our sample contained the best available evidence. Finally, overlap of each systematic review was assessed using Corrected Covered Area (CCA) to look at redundancy and research waste among the systematic reviews published on the topic. RESULTS: After screening, 12 studies were included in our sample. For the Oxford Levels of Evidence, we found that all the studies were Level I evidence. For the QUORUM assessment, we had 1 study with the highest score of 18. Additionally, we did the Oxman and Guyatt assessment, where we found 4 studies with a maximum score of 6. Finally, we did an AMSTAR assessment and found 2 studies with a score of 9. After conducting the methodological scores; the authors determined that Li. L et al 2021 had the highest quality. In addition, it was found that the CCA found among the primary studies in each systematic review calculated to .22. Any CCA above .15 is considered "very high overlap". CONCLUSIONS: The best available evidence suggests that Cemented HAs are better at preventing Prosthesis-related complications. Conversely, the best evidence also suggests that Cemented HA also results in longer operative time and increased intraoperative blood loss. When conducting future systematic reviews related to the topic, we ask that authors restrict conducting another systematic review until new evidence emerges so as not to confuse the clinical decision-making of physicians.

Spiritual Care Professionals as Unit-Based Interdisciplinary Team Members? Considering Patient and Staff Perceptions in a Forensic Mental Health Care Setting.

This project considers two co-occurring studies accounting perceptions of patients (n=8) and staff (n=8) related to assignment of Spiritual Care students as full-time interdisciplinary team members at a Forensic mental health facility. Students on 12-week placements were individually assigned to care units. Qualitative method consistent with Interpretative Phenomenological Analysis was employed. The co-occurring studies identified that enhanced access to Spiritual Care was valued. Staff and patients indicated a desire for more spirituality focused participation.

Reoperation and Complication Rates Following Patellar Fracture Repair with Plates: A Retrospective Analysis with Patient-Reported Outcomes at More than 1 Year of Follow-up.

Recent work has suggested good clinical and functional results with dorsal surface plating of patellar fractures. The primary outcome measurement of this study was reoperation rates for patellar fractures that had been treated with dorsal plating. Methods: This work consists of a retrospective review of clinical and functional outcome data following repair of patellar fractures with dorsal plates. We obtained institutional review board approval for this study and conducted a review of 9 consecutive years of our group's trauma practice. We also contacted patients to assess patient-reported outcomes (PROs) after 12 months. Results: Eighty-five patellar fractures were treated with open reduction and internal fixation (ORIF) via plating over 9 years. Eight (9.41%) of the patients required reoperation. Of the 72 patients with complete follow-up of ≥12 weeks, 3 (4.17%) had nonunion of the fracture site and 4 (5.56%) had loss of reduction of the fracture. The average Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score among our sample was 18.84 (slight symptoms); 72.41% of the patients in our sample had slight or no symptoms at ≥12 months postoperatively. Conclusions: Our results indicated that plating of comminuted patellar fractures is a safe, viable treatment strategy. The PROs at ≥12 months of follow-up data were promising. Additionally, dorsal plating may allow for early return of function and less postoperative bracing. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.