Introducing the Library of Guidance for Health Scientists (LIGHTS): A Living Database for Methods Guidance.

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance articles. Observations: Journal articles that aim to provide guidance for performing (including planning, design, conduct, analysis, and interpretation), reporting, and assessing the quality of health-related research involving humans or human populations (ie, excluding basic and animal research) are eligible for LIGHTS. A team of health researchers, information specialists, and methodologists continuously identifies and manually indexes eligible guidance documents. The search strategy includes focused searches of specific journals, specialized databases, and suggestions from researchers. A current limitation is that a keyword-based search of MEDLINE (and other general databases) and manual screening of records were not feasible because of the large number of hits (n = 915 523). As of September 20, 2022, LIGHTS included 1246 articles (336 reporting guidelines, 80 quality assessment tools, and 830 other methods guidance articles). The LIGHTS website provides a user-oriented search interface including filters for study type, specific methodological topic, research context, guidance type, and development process of the guidance. Automated matching of alternative methodological expressions (eg, enter loss to follow-up and find articles indexed with missing data) enhances search queries. Conclusions and Relevance: LIGHTS is a peer-supported initiative that is intended to increase access to and use of methods guidance relevant to health researchers, statisticians, methods consultants, methods developers, ethics boards, peer reviewers, journal editors, and funding bodies.

Evaluating the Role of Galectins in Clathrin-Independent Endocytosis.

Galectin-3 is a chimeric galectin involved in diverse intracellular and extracellular functions. Galectin-3 is synthesized in the cytoplasm and then released extracellularly by a poorly understood non-canonical secretion mechanism. As a result, it can play important roles both inside and outside the cell. One important extracellular role of galectin-3 is in modulating clathrin-independent endocytosis (CIE), a form of cellular internalization that is still not well understood. CIE, unlike clathrin-mediated endocytosis, has neither defined signaling sequences nor cytoplasmic machinery. As a result, extracellular interactions like the galectin-glycan interactions are thought to directly drive changes in CIE. This chapter discusses the methods designed to study the role of galectin-glycan interactions in CIE, which have provided us with insight into the functions of galectin-3 and cell surface glycans during CIE cargo internalization. These methods include media supplementation for metabolic glycoengineering, antibody internalization assays, lectin panels to assay changes in glycan patterns, exogenous galectin-3 supplementation, galectin-3 secretion assays, and in vitro assays to monitor the effect of galectins on CIE.

Prevalence of Avoidable and Bias-Inflicting Methodological Pitfalls in Real-World Studies of Medication Safety and Effectiveness.

Many real-word evidence (RWE) studies that utilize existing healthcare data to evaluate treatment effects incur substantial but avoidable bias from methodologically flawed study design; however, the extent of preventable methodological pitfalls in current RWE is unknown. To characterize the prevalence of avoidable methodological pitfalls with potential for bias in published claims-based studies of medication safety or effectiveness, we conducted an English-language search of PubMed for articles published from January 1, 2010 to May 20, 2019 and randomly selected 75 studies (10 case-control and 65 cohort studies) that evaluated safety or effectiveness of cardiovascular, diabetes, or osteoporosis medications using US health insurance claims. General and methodological study characteristics were extracted independently by two reviewers, and potential for bias was assessed across nine bias domains. Nearly all studies (95%) had at least one avoidable methodological issue known to incur bias, and 81% had potentially at least one of the four issues considered major due to their potential to undermine study validity: time-related bias (57%), potential for depletion of outcome-susceptible individuals (44%), inappropriate adjustment for postbaseline variables (41%), or potential for reverse causation (39%). The median number of major issues per study was 2 (interquartile range (IQR), 1-3) and was lower in cohort studies with a new-user, active-comparator design (median 1, IQR 0-1) than in cohort studies of prevalent users with a nonuser comparator (median 3, IQR 3-4). Recognizing and avoiding known methodological study design pitfalls could substantially improve the utility of RWE and confidence in its validity.

Prevention and Management of Pseudoverrucous Lesions: A Review and Case Scenarios.

GENERAL PURPOSE: To present the associated risk factors, prevention measures, and assessment and management of pseudoverrucous lesions specific to a surgically created ileal conduit, as well as three clinical scenarios illustrating this condition. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Define pseudoverrucous lesions.2. Identify the risk factors for stoma complications such as pseudoverrucous lesions.3. Select the appropriate routine care procedures to teach patients following stoma creation to help prevent pseudoverrucous lesions.4. Choose the recommended treatment options for patients who develop pseudoverrucous lesions.

Pseudoverrucous lesions are a late peristomal complication that occurs most commonly in people with urinary stomas. Impairment of the peristomal skin can result in pouching system leaks that can translate into odor, embarrassment, and diminished quality of life. Prevention is key to maintaining smooth, dry skin and intact psyche. Treatment revolves around outpatient postoperative follow-up, refitting the pouching system to eliminate moisture impacting the peristomal area, modification of pouching system wear time, acidification of the urine, and intensive education. This review includes three case scenarios to support early, intermediate, and late-stage intervention guidelines. Some interventions were successful; one case remains unresolved.

A Comprehensive Comparison and Validation of Published Methods to Detect Turn Switch during Alpine Skiing.

The instant of turn switch (TS) in alpine skiing has been assessed with a variety of sensors and TS concepts. Despite many published methodologies, it is unclear which is best or how comparable they are. This study aimed to facilitate the process of choosing a TS method by evaluating the accuracy and precision of the methodologies previously used in literature and to assess the influence of the sensor type. Optoelectronic motion capture, inertial measurement units, pressure insoles, portable force plates, and electromyography signals were recorded during indoor treadmill skiing. All TS methodologies were replicated as stated in their respective publications. The method proposed by Supej assessed with optoelectronic motion capture was used as a comparison reference. TS time differences between the reference and each methodology were used to assess accuracy and precision. All the methods analyzed showed an accuracy within 0.25 s, and ten of them within 0.05 s. The precision ranged from ~0.10 s to ~0.60 s. The TS methodologies with the best performance (accuracy and precision) were Klous Video, Spörri PI (pressure insoles), Martinez CTD (connected boot), and Yamagiwa IMU (inertial measurement unit). In the future, the specific TS methodology should be chosen with respect to sensor selection, performance, and intended purpose.

Outcomes from a multimodal, at-scale community-based HIV counselling and testing programme in twelve high HIV burden districts in South Africa.

INTRODUCTION: Facility-based HIV testing services (HTS) have been less acceptable and accessible by adolescents, men and key populations in South Africa. Community-based HIV counselling and testing (CBCT) modalities, including mobile unit and home-based testing, have been proposed to decrease barriers to HIV testing uptake. CBCT modalities and approaches may be differentially acceptable to men and women based on age. Implementation of multimodal CBCT services may improve HIV testing rates among adolescents and men, and support the roll-out of prevention services. METHODS: A cross-sectional analysis was conducted using aggregate, routine programmatic data collected from 1 October 2015 through 31 March 2017 from a multimodal, at-scale CBCT programme implemented in 12 high-burden districts throughout South Africa. Data collection tools were aligned to reporting standards for the National Department of Health and donor requirements. HIV testing rates (i.e. number of tests performed per 100,000 population using South African census data) and testing proportions by modality were stratified by sex, age groups and heath districts. Descriptive statistics were performed using STATA 13.0. RESULTS: Overall, 944,487 tests were performed during the 1.5-year testing period reported. More tests were conducted among females than males (53.6% vs. 46.4%). Overall, 8206 tests per 100,000 population (95% CI: 8190.2 to 8221.9) were performed; female-to-male (F:M) testing ratio was 1.11. Testing rates were highest among young women age 20 to 24 years (16,328.4; 95% CI: 16,237.9 to 16,419.1) and adolescent girls aged 15 to 19 years (12,817.0; 95% CI: 12,727.9 to 12,906.6). Home-based testing accounted for 61.3% of HIV tests, followed by near-home mobile unit testing (30.2%) and workplace mobile unit testing (4.7%). More women received HTS via home-based testing (F:M ratio = 1.29), whereas more men accessed work-place mobile testing (M:F ratio = 1.35). No sex differential was observed among those accessing near-home mobile testing (F:M ratio = 0.98). CONCLUSIONS: Concurrent implementation of multiple, targeted CBCT modalities can reduce sex disparities in HIV testing in South Africa. Given the acceptability and accessibility of these CBCT services to adolescent girls and young women, evident from their high testing rates, leveraging community-based services delivery platforms to increase access to HIV prevention services, including pre-exposure prophylaxis (PrEP), should be considered.

Methodological quality was critically low in 9/10 systematic reviews in advanced cancer patients-A methodological study.

OBJECTIVE: To assess the methodological quality and the consideration of heterogeneity in systematic reviews (SRs). STUDY DESIGN AND SETTING: We conducted a methodological study (CRD42019134904) and searched three databases from January 2010 to July 2019. Interventional SRs with a statistically significant meta-analysis of at least four randomized controlled trials in advanced cancer patients were included. A MeaSurement Tool to Assess Systematic Reviews (AMSTAR) 2 was used to evaluate the SRs' methodological quality. The consideration of heterogeneity was categorized in clinical or/and methodological heterogeneity and not explored. RESULTS: From 6234 identified references, 261 SRs were included. Most SRs had a critically low quality (230, 88.1%). The majority of them (209, 80.1%) was classified as critically low because of non-registration (222, 85.1%) combined with the non-reporting of excluded full-texts and missing justifications for exclusion (218, 83.5%). Heterogeneity in trial results was not explored at all in 51 (19.5%) SRs whereas clinical heterogeneity was considered in 117 (44.8%), methodological heterogeneity in 13 (5.0%), and both clinical and methodological heterogeneity in 80 (30.7%) SRs. CONCLUSION: The consideration of these findings in trainings for review authors and peer reviewers could improve the awareness of quality criteria and the quality of future SRs. TRIAL REGISTRATION: PROSPERO-ID: CRD42019134904.

Ten simple rules on how to write a standard operating procedure.

Research publications and data nowadays should be publicly available on the internet and, theoretically, usable for everyone to develop further research, products, or services. The long-term accessibility of research data is, therefore, fundamental in the economy of the research production process. However, the availability of data is not sufficient by itself, but also their quality must be verifiable. Measures to ensure reuse and reproducibility need to include the entire research life cycle, from the experimental design to the generation of data, quality control, statistical analysis, interpretation, and validation of the results. Hence, high-quality records, particularly for providing a string of documents for the verifiable origin of data, are essential elements that can act as a certificate for potential users (customers). These records also improve the traceability and transparency of data and processes, therefore, improving the reliability of results. Standards for data acquisition, analysis, and documentation have been fostered in the last decade driven by grassroot initiatives of researchers and organizations such as the Research Data Alliance (RDA). Nevertheless, what is still largely missing in the life science academic research are agreed procedures for complex routine research workflows. Here, well-crafted documentation like standard operating procedures (SOPs) offer clear direction and instructions specifically designed to avoid deviations as an absolute necessity for reproducibility. Therefore, this paper provides a standardized workflow that explains step by step how to write an SOP to be used as a starting point for appropriate research documentation.

Protocol for Investigating the Interactions Between Intrinsically Disordered Proteins and Membranes by Neutron Reflectometry.

Several intrinsically disordered proteins (IDPs) exhibit high affinity for lipid membranes. Among the different biophysical methods to probe protein-lipid interaction, neutron reflectometry (NR) can provide direct and structural detailed information on the location of the IDP with respect to the membrane. Supported lipid bilayers are commonly used as cell membrane models in such experiments. NR measurements can be collected on the supported lipid bilayer before and after the interaction with the IDP to characterize whether the protein molecules are mainly located on the membrane surface (interaction with the lipid headgroups), are penetrating into the hydrophobic region of the membrane (interaction with the lipid acyl chains), or are not interacting at all with the membrane. The lipid composition of the supported lipid bilayer can easily be tuned; hence the NR experiments can be designed to investigate selective IDP-lipid interactions.This chapter will describe the fundamental steps for performing an NR experiment and the subsequent data analysis aimed at characterizing IDP-lipid bilayer interactions. The specific case of an intrinsically disordered region (IDR) from the membrane protein Na+/H+ exchanger isoform 1 (NHE1) will be used as an example, but the same protocol can be easily adapted to other IDPs.

Impact of integrated graphical display on expert and novice diagnostic performance in critical care.

OBJECTIVE: To determine the impact of a graphical information display on diagnosing circulatory shock. MATERIALS AND METHODS: This was an experimental study comparing integrated and conventional information displays. Participants were intensivists or critical care fellows (experts) and first-year medical residents (novices). RESULTS: The integrated display was associated with higher performance (87% vs 82%; P < .001), less time (2.9 vs 3.5 min; P = .008), and more accurate etiology (67% vs 54%; P = .048) compared to the conventional display. When stratified by experience, novice physicians using the integrated display had higher performance (86% vs 69%; P < .001), less time (2.9 vs 3.7 min; P = .03), and more accurate etiology (65% vs 42%; P = .02); expert physicians using the integrated display had nonsignificantly improved performance (87% vs 82%; P = .09), time (2.9 vs 3.3; P = .28), and etiology (69% vs 67%; P = .81). DISCUSSION: The integrated display appeared to support efficient information processing, which resulted in more rapid and accurate circulatory shock diagnosis. Evidence more strongly supported a difference for novices, suggesting that graphical displays may help reduce expert-novice performance gaps.

Validation of educational material for the care of people with intestinal stoma.

OBJECTIVE: to validate an educational booklet for people with intestinal stoma as a technological resource in the teaching of self-care. METHOD: a methodological research for the construction and validation of an educational booklet by nine expert judges and 25 people with stomas. The agreement index of at least 80% was considered to guarantee the validation of the material. RESULTS: regarding the objectives of the booklet, all the judges evaluated the items as "adequate" or "totally adequate", with a content validity index of 1.00. Regarding the structure and presentation of the booklet, the total index was 0.84. Regarding relevance, the total was 0.97 and the general index of the educational booklet was 0.89, confirming the validation with the judges. All items of the organization, writing style, appearance and motivation of the material were considered as validated by the target audience, reaching a total agreement index of 0.99. CONCLUSION: in the context of health education, the booklet was considered valid and suitable for the care of people with intestinal stoma, and can be used in teaching, research, extension and care for people with intestinal stoma.

General Pediatricians' Performance of Accreditation Agency's Recommended Procedures: A Complementary Analysis Using Administrative Data and the Knowledge Translation Model.

INTRODUCTION: The Accreditation Council for Graduate Medical Education provided guidelines, in 2013, regarding 13 clinical procedures pediatric residents should learn. Previous studies show that, when asked, general pediatricians (GPeds) self-report performing these procedures infrequently. When examined using the knowledge translation model, this low procedural performance frequency, especially by GPeds, may indicate a problem within the primary care landscape. METHODS: This was a descriptive study using the Partners For Kids, an accountable care organization, database to obtain how frequently each of the procedures was performed for a geographically representative sample of GPeds in central Ohio. RESULTS: A total of 296 physicians participated in Partners For Kids. Nearly one-third practiced for more than 15 years (n = 83, 28%) and one-third also lived in a rural region (n = 78, 26.4%). The most commonly billed procedure was administering immunizations (n = 79,292, 92.3%); the least was peripheral intravenous catheter placement (n = 2, 0.002%). Most procedures were completed in the office-based setting. DISCUSSION: General pediatricians in central Ohio do not frequently perform the 13 recommended procedures of Accreditation Council for Graduate Medical Education. Evaluation of this problem using the knowledge translation model shows that potential barriers could be inadequate training during or after residency or more likely that these procedures are not necessary in GPeds' current scope of practice. The next step should be to see, from the practitioner's perspective, what procedures are important to their daily practice. Adapting this knowledge to the local context will help target continuing medical education/continuing professional development interventions.

Efficient refolding and reconstitution of tissue factor into nanodiscs facilitates structural investigation of a multicomponent system on a lipid bilayer.

Structural data on membrane proteins in a lipid membrane environment is challenging to obtain but needed to provide information on the, often essential, protein-lipid interplay. A common experimental bottleneck in obtaining such data is providing samples in sufficient amounts and quality required for structural studies. We developed a new production protocol for the single-pass transmembrane protein (SPTMP) tissue factor (TF), exploiting the high expression level in E. coli inclusion bodies and subsequent refolding. This provided more than 5 mg of functional TF per liter bacterial culture. This is substantially more than what was obtained by the classical approaches for expressing TF in the membrane-anchored configuration. We optimized reconstitution into circularized nanodiscs enabling the formation of stable, TF loaded nanodiscs with different lipid compositions and with a limited material waste. The blood coagulation cascade is initiated by the complex formation between TF and Factor VIIa (FVIIa), and we probed this interaction by a functional assay and SPR measurements, which revealed similar activity and binding kinetics as TF produced by other protocols, demonstrating that high-yield production does not compromise TF function. Furthermore, the amounts of sample produced permitted initial small angle X-ray scattering studies providing the first structural information about TF and its binding to FVIIa in a lipid environment. This strategy possibly allows for probing the multicomponent complex TF:FVIIa together with its substrate Factor X on a lipid bilayer, but may also be relevant as a production strategy for other SPTMP for which structural information, in general, is limited.

Development of a simple method for differential delivery of volatile anesthetics to the spinal cord of the rabbit.

Emulsified volatile anesthetic can be directly injected into the circulation and eliminated from blood through lungs. Taking advantage of the unique pharmacokinetics of the emulsified volatile anesthetics, we aimed to develop a less traumatic method to differentially deliver them to the spinal cord of rabbit. Sixteen New Zealand White rabbits were randomly assigned to the isoflurane or sevoflurane group. A catheter was placed into the descending aorta, and emulsified isoflurane (8mg/kg/h) or sevoflurane (12mg/kg/h) was given respectively. The concentration and partial pressure of the anesthetics in the jugular and femoral vein were measured. Our results showed that the partial pressure for isoflurane was 3.91±1.11 mmHg and 12.61±1.60 mmHg (1.0MAC), and for sevoflurane was 3.89±1.00 mmHg and 19.92±1.84mmHg (1.0MAC), in the jugular vein and femoral vein, respectively. There was significant difference between jugular and femoral vein partial pressure for both isoflurane and sevoflurane groups (both P < 0.001). In conclusion, a simple and minimally invasive method has been successfully developed to selectively deliver isoflurane and sevoflurane to the spinal cord in the rabbit. Before the anesthetics taking action on the brain, 69% of isoflurane and 81% of sevoflurane were removed through lungs. This method can be used to investigate sites and mechanisms of volatile anesthetic action.