Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Transcutaneous Electrical Nerve Stimulation (TENS) for Chronic Primary Low Back Pain in Adults.

PURPOSE: To evaluate benefits and harms of transcutaneous electrical nerve stimulation (TENS) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: We searched for randomized controlled trials (RCTs) from various electronic databases from July 1, 2007 to March 9, 2022. Eligible RCTs targeted TENS compared to placebo/sham, usual care, no intervention, or interventions with isolated TENS effects (i.e., combined TENS with treatment B versus treatment B alone) in adults with CPLBP. We extracted outcomes requested by the WHO Guideline Development Group, appraised the risk of bias, conducted meta-analyses where appropriate, and graded the certainty of evidence using GRADE. RESULTS: Seventeen RCTs (adults, n = 1027; adults ≥ 60 years, n = 28) out of 2010 records and 89 full text RCTs screened were included. The evidence suggested that TENS resulted in a marginal reduction in pain compared to sham (9 RCTs) in the immediate term (2 weeks) (mean difference (MD) = -0.90, 95% confidence interval -1.54 to -0.26), and a reduction in pain catastrophizing in the short term (3 months) with TENS versus no intervention or interventions with TENS specific effects (1 RCT) (MD = -11.20, 95% CI -17.88 to -3.52). For other outcomes, little or no difference was found between TENS and the comparison interventions. The certainty of the evidence for all outcomes was very low. CONCLUSIONS: Based on very low certainty evidence, TENS resulted in brief and marginal reductions in pain (not deemed clinically important) and a short-term reduction in pain catastrophizing in adults with CPLBP, while little to no differences were found for other outcomes.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Needling Therapies for Chronic Primary Low Back Pain in Adults.

PURPOSE: Evaluate benefits and harms of needling therapies (NT) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing NT compared with placebo/sham, usual care, or no intervention (comparing interventions where the attributable effect could be isolated). We conducted meta-analyses where indicated and graded the certainty of evidence. RESULTS: We screened 1831 citations and 109 full text RCTs, yeilding 37 RCTs. The certainty of evidence was low or very low across all included outcomes. There was little or no difference between NT and comparisons across most outcomes; there may be some benefits for certain outcomes. Compared with sham, NT improved health-related quality of life (HRQoL) (physical) (2 RCTs; SMD = 0.20, 95%CI 0.07; 0.32) at 6 months. Compared with no intervention, NT reduced pain at 2 weeks (21 RCTs; MD = - 1.21, 95%CI - 1.50; - 0.92) and 3 months (9 RCTs; MD = - 1.56, 95%CI - 2.80; - 0.95); and reduced functional limitations at 2 weeks (19 RCTs; SMD = - 1.39, 95%CI - 2.00; - 0.77) and 3 months (8 RCTs; SMD = - 0.57, 95%CI - 0.92; - 0.22). In older adults, NT reduced functional limitations at 2 weeks (SMD = - 1.10, 95%CI - 1.71; - 0.48) and 3 months (SMD = - 1.04, 95%CI - 1.66; - 0.43). Compared with usual care, NT reduced pain (MD = - 1.35, 95%CI - 1.86; - 0.84) and functional limitations (MD = - 2.55, 95%CI - 3.70; - 1.40) at 3 months. CONCLUSION: Based on low to very low certainty evidence, adults with CPLBP experienced some benefits in pain, functioning, or HRQoL with NT; however, evidence showed little to no differences for other outcomes.

Investigating force-time characteristics of prone thoracic SMT and self-reported patient outcome measures: a feasibility study.

BACKGROUND: Spinal manipulative therapy (SMT) is commonly used to treat musculoskeletal conditions, including thoracic spine pain. Applying patient-specific force-time characteristics are believed to be important to improve SMT's effectiveness. Investigating SMT as part of a multimodal approach is fundamental to account for the complexity of chiropractic clinical practice. Therefore, pragmatic investigations balancing minimal disruptions to the clinical encounter at the same time as ensuring a robust data quality with rigorous protocols are needed. Consequently, preliminary studies are required to assess the study protocol, quality of data recorded and the sustainability of such investigation. Therefore, this study examined the feasibility of investigating SMT force-time characteristics and clinical outcome measures in a clinical setting. METHODS: In this mixed-methods study, providers recorded thoracic SMT force-time characteristics delivered to patients with thoracic spinal pain during regular clinical encounters. Self-reported clinical outcomes of pain, stiffness, comfort during the SMT (using an electronic visual analogue scale), and global rating of change scale were measured before and after each SMT application. Feasibility was quantitatively assessed for participant recruitment, data collection and data quality. Qualitative data assessed participants' perceptions on the impact of data collection on patient management and clinical flow. RESULTS: Twelve providers (58% female, 27.3 ± 5.0 years old) and twelve patients (58% female, 37.2 ± 14.0 years old) participated in the study. Enrolment rate was greater than 40%, data collection rate was 49% and erroneous data was less than 5%. Participant acceptance was good with both providers and patients reporting positive experience with the study. CONCLUSIONS: Recording SMT force-time characteristics and self-reported clinical outcome measures during a clinical encounter may be feasible with specific modification to the current protocol. The study protocol did not negatively impact patient management. Specific strategies to optimize the data collection protocol for the development of a large clinical database are being developed.

Derrone Targeting the TGF Type 1 Receptor Kinase Improves Bleomycin-Mediated Pulmonary Fibrosis through Inhibition of Smad Signaling Pathway.

Transforming growth factor-ß (TGF-ß) has a strong impact on the pathogenesis of pulmonary fibrosis. Therefore, in this study, we investigated whether derrone promotes anti-fibrotic effects on TGF-ß1-stimulated MRC-5 lung fibroblast cells and bleomycin-induced lung fibrosis. Long-term treatment with high concentrations of derrone increased the cytotoxicity of MRC-5 cells; however, substantial cell death was not observed at low concentrations of derrone (below 0.05 µg/mL) during a three-day treatment. In addition, derrone significantly decreased the expressions of TGF-ß1, fibronectin, elastin, and collagen1α1, and these decreases were accompanied by downregulation of α-SMA expression in TGF-ß1-stimulated MRC-5 cells. Severe fibrotic histopathological changes in infiltration, alveolar congestion, and alveolar wall thickness were observed in bleomycin-treated mice; however, derrone supplementation significantly reduced these histological deformations. In addition, intratracheal administration of bleomycin resulted in lung collagen accumulation and high expression of α-SMA and fibrotic genes-including TGF-ß1, fibronectin, elastin, and collagen1α1-in the lungs. However, fibrotic severity in intranasal derrone-administrated mice was significantly less than that of bleomycin-administered mice. Molecular docking predicted that derrone potently fits into the ATP-binding pocket of the TGF-ß receptor type 1 kinase domain with stronger binding scores than ATP. Additionally, derrone inhibited TGF-ß1-induced phosphorylation and nuclear translocations of Smad2/3. Overall, derrone significantly attenuated TGF-ß1-stimulated lung inflammation in vitro and bleomycin-induced lung fibrosis in a murine model, indicating that derrone may be a promising candidate for preventing pulmonary fibrosis.

Therapeutic Dance for the Healing of Sexual Trauma: A Systematic Review.

Therapeutic dance has been increasingly used as a treatment modality for sexual trauma, yet its evidence-based efficacy has not yet been catalogued. We therefore conducted a systematic review to summarize the existing evidence for therapeutic dance as an intervention for healing after sexual trauma. We searched 5 major databases to identify intervention studies on the use of therapeutic dance for individuals with histories of sexual trauma. Studies were included based on the following criteria: 1) the study involves individuals who have been exposed to sexual trauma; 2) the study reports on any form of dance as a therapeutic intervention; and 3) the study reports on dance intervention outcomes. A total of 1,686 sources were identified. Of these, 11 articles met eligibility criteria and were assessed. Reported outcomes were extracted and organized into emergent domains. We found that therapeutic dance acts upon three broad domains-affect, self, and interpersonal relationships - and can be delivered in diverse settings. Across the studies, dance showed benefits on outcomes. However, a significant weakness of the current peer-reviewed literature is the lack of robust empirical intervention research on dance therapy. Overall, the emerging literature suggests that therapeutic dance is a potential intervention for those who have experienced sexual trauma. The review findings presented here can be used to inform practitioners and systems of care targeted for those who have been subject to sexual trauma.

A contiguous de novo genome assembly of sugar beet EL10 (Beta vulgaris L.).

A contiguous assembly of the inbred 'EL10' sugar beet (Beta vulgaris ssp. vulgaris) genome was constructed using PacBio long-read sequencing, BioNano optical mapping, Hi-C scaffolding, and Illumina short-read error correction. The EL10.1 assembly was 540 Mb, of which 96.2% was contained in nine chromosome-sized pseudomolecules with lengths from 52 to 65 Mb, and 31 contigs with a median size of 282 kb that remained unassembled. Gene annotation incorporating RNA-seq data and curated sequences via the MAKER annotation pipeline generated 24,255 gene models. Results indicated that the EL10.1 genome assembly is a contiguous genome assembly highly congruent with the published sugar beet reference genome. Gross duplicate gene analyses of EL10.1 revealed little large-scale intra-genome duplication. Reduced gene copy number for well-annotated gene families relative to other core eudicots was observed, especially for transcription factors. Variation in genome size in B. vulgaris was investigated by flow cytometry among 50 individuals producing estimates from 633 to 875 Mb/1C. Read-depth mapping with short-read whole-genome sequences from other sugar beet germplasm suggested that relatively few regions of the sugar beet genome appeared associated with high-copy number variation.

Adherence to spinal imaging guidelines and utilization of lumbar spine diagnostic imaging for low back pain at a Canadian Chiropractic College: a historical clinical cohort study.

BACKGROUND: Diagnostic imaging is useful for assessing low back pain (LBP) when a clinician suspects a specific underlying pathology. Evidence-based imaging guidelines assist clinicians in appropriately determining the need for imaging when assessing LBP. A previous study reported high adherence to three clinical guidelines, with utilization rate of 12.3% in imaging of LBP patients attending a chiropractic teaching clinic. A new imaging guideline for spinal disorders has been published and used in teaching. Thus, the aims of our study were to assess the adherence to the new guideline and X-ray utilization in new episodes of LBP. METHODS: We conducted a historical clinical cohort study using patient electronic health record audits at seven teaching clinics over a period of 20 months. Records of patients who were at least 18 years of age, presented with a new onset of LBP, and consented to data collection were included. Abstracted data included patient demographics, the number and type of red flags, and the decision to image. Rate of guideline adherence (proportion of those not recommended for imaging, given no red flags) and rate of image utilization were descriptively analyzed. RESULTS: We included 498 patients in this study. At least 81% of included patients had one or more red flags reported. The most commonly reported individual red flag was age ≥ 50 (43.8%) followed by pain at rest (15.7%). In those referred for imaging, age ≥ 50 (93.3%) was the most frequently reported red flag. No red flag(s) were identified in 93 patient records, and none were referred for imaging of their LBP, yielding an adherence rate of 100% (95% CI 96, 100%). A total of 17 of 498 patients were recommended for imaging for their low back pain, resulting in an imaging utilization rate of 3.4% (95% CI 1.8, 5.0%). CONCLUSION: The imaging utilization rate was 3.4%, lower than 12.3% previously reported at a chiropractic teaching clinic. None without red flags were referred for imaging, yielding a 100%, adherence rate to current LBP imaging guidelines. Future research should consider currency of guideline, accuracy of red flags and factors influencing clinicians' decision, when assessing imaging adherence rates.

Exploring clinician perceptions of a care pathway for the management of shoulder pain: a qualitative study.

BACKGROUND: Clinical care pathways may be useful tools to improve the quality of healthcare by facilitating the translation of evidence into practice. Our study is situated within a larger project, whereby end-users co-developed a care pathway for the management of shoulder pain. In this study, we explored end-user perceptions of the usefulness and practicality of implementing a care pathway to manage shoulder pain. We also solicited feedback for the pathway's improvement. METHODS: We conducted a qualitative study using a transcendental phenomenological approach seen through a constructivist lens. Clinicians recorded themselves interacting with the care pathway while working through a clinical case. Clinicians described their thoughts and movements aloud as they completed the activity. Second, we conducted individual semi-structured interviews to discuss the usefulness and practicality of pathway implementation. Interview transcripts were coded independently by reviewers. Transcript codes and associated quotes were grouped into themes. Themes were sequenced and linked creating a 'web' of thematic connections. Summary statements were developed to synthesize the overall essence of the phenomena. RESULTS: Nine clinicians participated. Participants included eight chiropractors and one medical physician. We found that clinicians believed the care pathway could be useful at various levels, including education (students, interns), for early career clinicians, for engaging patients, facilitating interprofessional communication, and as a reminder of information for certain, less familiar conditions. When discussing the practicality of implementing the care pathway into practice settings, clinicians expressed that agreement with the care pathway and its recommendations may influence its acceptability among clinicians. Additionally, integrating recommendations into practice may be a skill requirement included into clinical training. Clinicians described the importance of opinion leaders in the acceptability of new evidence. Various difficulties with the replicability of interventions into clinical care was also discussed. In general, clinicians suggested the layout of the care pathway was manageable, and there was sufficient information for clinical decision-making. Clinicians also made several recommendations for improvement. CONCLUSIONS: End-user involvement and collaboration provides tangible instruction to improve care pathways themselves, their implementation strategies and helps to support and strengthen future research for overcoming individual, systemic and contextual barriers.

Promoting the use of a self-management strategy among novice chiropractors treating individuals with spine pain: A mixed methods pilot clustered-clinical trial.

BACKGROUND: The uptake of Self-Management Support (SMS) among clinicians is suboptimal. To date, few studies have tested knowledge translation (KT) interventions to increase the application of SMS in chiropractic teaching clinics. STUDY OBJECTIVE: Evaluate the feasibility of implementing a KT intervention to promote the use of a SMS strategy among chiropractic interns, their supervisors, and individuals with spine pain compared to controls. METHODS: Mixed methods pilot clustered-clinical trial. Clusters of 16 Patient Management Teams were allocated to a complex KT intervention (online and workshop training). Primary feasibility outcomes for clinicians, interns and patients were rates of recruitment, retention, and adherence to protocol. A nominal group technique and interviews were used to seek end-users' views on the implementation process, and generate possible solutions. RESULTS: In total, 16 (84%) clinicians, 65 (26%) interns and 42 patients agreed to participate. All clinicians in the intervention group completed all KT intervention components, 23 interns (85%) completed the online training and 14 interns (51.8%) attended the workshop training. All clinicians in the intervention and seven (78%) in the control group completed all outcome measures at baseline and 6-month follow-up, while 15 (55.6%) and 23 (60.5%) interns in the intervention and control groups completed the questionnaires at baseline and 6-month follow-up, respectively. Among patients, 10 (52.6%) and 12 (52.2%) in the intervention and control groups respectively completed the questionnaires at the end of the study. Based on interview findings, solutions to improve the feasibility of conducting a full trial include: making SMS a part of the internship, changing the time of introducing the study to the interns, and having more training on SMS. CONCLUSION: Recruitment and retention of chiropractic interns and patients for a larger implementation trial in a single outpatient teaching clinic may be challenging.

Best-Practice Recommendations for Chiropractic Care for Pregnant and Postpartum Patients: Results of a Consensus Process.

OBJECTIVE: The purpose of this project was to develop a best-practices document on chiropractic care for pregnant and postpartum patients with low back pain (LBP), pelvic girdle pain (PGP), or a combination. METHODS: A modified Delphi consensus process was conducted. A multidisciplinary steering committee of 11 health care professionals developed 71 seed statements based on their clinical experience and relevant literature. A total of 78 panelists from 7 countries were asked to rate the recommendations (70 chiropractors and representatives from 4 other health professions). Consensus was reached when at least 80% of the panelists deemed the statement to be appropriate along with a median response of at least 7 on a 9-point scale. RESULTS: Consensus was reached on 71 statements after 3 rounds of distribution. Statements included informed consent and risks, multidisciplinary care, key components regarding LBP during pregnancy, PGP during pregnancy and combined pain during pregnancy, as well as key components regarding postpartum LBP, PGP, and combined pain. Examination, diagnostic imaging, interventions, and lifestyle factors statements are included. CONCLUSION: An expert panel convened to develop the first best-practice consensus document on chiropractic care for pregnant and postpartum patients with LBP or PGP. The document consists of 71 statements on chiropractic care for pregnant and postpartum patients with LBP and PGP.

Characterization of thoracic spinal manipulation and mobilization forces in older adults.

BACKGROUND: Spinal mobilization and spinal manipulation are common interventions used by manual therapists to treat musculoskeletal conditions in older adults. Their force-time characteristics applied to older adults' thoracic spine are important considerations for effectiveness and safety but remain unknown. This study aimed to describe the force-time characteristics of posterior-to-anterior spinal mobilization and manipulation delivered to older adults' thoracic spine. METHODS: Twenty-one older adults (≥65 years) with no thoracic pain received posterior-to-anterior thoracic spinal mobilization and/or manipulation with the force characteristics a chiropractor deemed appropriate. Six-degree-of-freedom load cells and an instrumented treatment table recorded the force characteristics of both interventions at the clinician-participant and participant-table interfaces, respectively. Preload force, total peak force, time to peak and loading rate were analyzed descriptively. FINDINGS: Based on data from 18 adults (56% female; average: 70 years old), mean resultant spinal mobilization forces at the clinician-participant interface were: 220 ± 51 N during preload, 323 ± 67 N total peak force, and 312 ± 38 ms time to peak. At the participant-table interface, mobilization forces were 201 ± 50 N during preload, 296 ± 63 N total peak force, and 308 ± 44 ms time to peak. Mean resultant spinal manipulation forces at the clinician-participant interface were: 260 ± 41 N during preload, 470 ± 46 N total peak force, and 165 ± 28 ms time to peak. At the participant table interface, spinal manipulation forces were 236 ± 47 N during preload, 463 ± 57 N total peak force, and 169 ± 28 ms time to peak. INTERPRETATION: Results suggest older adults experience unique, but comparable force-time characteristics during spinal mobilization and manipulation delivered to their thoracic spine compared to the ones delivered to younger adults described in the literature.

Erratum. Establishment of the T1D Exchange Quality Improvement Collaborative (T1DX-QI). Clinical Diabetes 2020;38:141-151 (DOI: 10.2337/cd19-0032).

[This corrects the article on p. 141 in vol. 38, PMID: 32327886.].

Establishment of the T1D Exchange Quality Improvement Collaborative (T1DX-QI).

The T1D Exchange established a learning platform by evaluating the current state of care and engaging 10 diabetes clinics in collaborative quality improvement (QI) activities. Participating clinics are sharing data and best practices to improve care delivery for people with type 1 diabetes. This article describes the design and initial implementation of this platform, known as the T1D Exchange Quality Improvement Collaborative. This effort has laid a foundation for learning from variation in type 1 diabetes care delivery via QI methodology and has demonstrated success in improving processes through iterative testing cycles and transparent sharing of data.

Microfluidic-Enabled Print-to-Screen Platform for High-Throughput Screening of Combinatorial Chemotherapy.

Since the 1960s, combination chemotherapy has been widely utilized as a standard method to treat cancer. However, because of the potentially enormous number of drug candidates and combinations, conventional identification methods of the effective drug combinations are usually associated with significantly high operational costs, low throughput screening, laborious and time-consuming procedures, and ethical concerns. In this paper, we present a low-cost, high-efficiency microfluidic print-to-screen (P2S) platform, which integrates combinatorial screening with biomolecular printing for high-throughput screening of anticancer drug combinations. This P2S platform provides several distinct advantages and features, including automatic combinatorial printing, high-throughput parallel drug screening, modular disposable cartridge, and biocompatibility, which can potentially speed up the entire discovery cycle of potent drug combinations. Microfluidic impact printing utilizing plug-and-play microfluidic cartridges is experimentally characterized with controllable droplet volume and accurate positioning. Furthermore, the combinatorial print-to-screen assay is demonstrated in a proof-of-concept biological experiment which can identify the positive hits among the entire drug combination library in a parallel and rapid manner. Overall, this microfluidic print-to-screen platform offers a simple, low-cost, high-efficiency solution for high-throughput large-scale combinatorial screening and can be applicable for various emerging applications in drug cocktail discovery.

Comprehensive care of the patient with idiopathic pulmonary fibrosis.

PURPOSE OF REVIEW: Recently, an expert committee endorsed by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society published an evidence-based guideline on the management of idiopathic pulmonary fibrosis (IPF). In the current document, we summarize and supplement this recent expert document and propose a comprehensive approach to the care and management of patients with IPF. RECENT FINDINGS: We propose three pillars of care for the patient with IPF titled 'disease-centered management', 'symptom-centered management', and 'education and self-management'. Disease-centered management involves both pharmacological and nonpharmacological approaches. Palliative care should be an integral and routine component of the care of patients with IPF. Education and self-management strengthens the provider-patient partnership by enabling patients to set realistic goals, remain in control of his or her care, and prepare for the future. SUMMARY: The comprehensive care of the patient with IPF involves balancing the three pillars of disease-centered management, symptom-centered management, and patient education and self-management upon a solid foundation of provider-patient partnership. Constant reassessment of the individual patient's goals of care, based on their values and preferences, is essential to the constant recalibration of these various interventions.

Extensive hyperpigmented plaques in a chinese singaporean woman: a case of cutaneous plasmacytosis.

Cutaneous plasmacytosis is a rare disease entity presenting with multiple extensive red-brown plaques, histopathology showing marked hyperplasia of mature polyclonal plasma cells, and polyclonal hypergammaglobulinemia on serum protein electrophoresis, in the absence of an underlying secondary cause. We report in this article the first case of cutaneous plasmacytosis from Singapore. A 33-year-old Chinese woman presented with mildly pruritic reddish brown papules and plaques over her trunk and arms for 2 years. Physical examination, laboratory investigations, and radiographic examination were negative for systemic involvement and lymphadenopathy. Serum immunoelectrophoresis showed polyclonal hypergammaglobulinemia with immunoglobulin G and immunoglobulin A. Two sets of skin biopsies performed 2 years apart essentially showed similar histopathological findings of a superficial and deep perivascular infiltrate with numerous mature plasma cells and small typical lymphocytes. There were lymphoid follicles with well-formed germinal centers and mantle zones, surrounded by mature lymphocytes. No light chain restriction was present on immunohistochemistry, and polymerase chain reaction for heavy chain gene rearrangement was negative for monoclonality. Despite potent topical corticosteroids and 8 months of phototherapy with narrow band ultraviolet light, there was no improvement. Intralesional triamcinolone injections to a few lesions afforded temporary relief of itch and flattening of lesions.