Rehabilitation of back pain in the pediatric population: a mixed studies systematic review.

BACKGROUND: A significant proportion of children and adolescents experience back pain. However, a comprehensive systematic review on the effectiveness of rehabilitation interventions is lacking. OBJECTIVES: To evaluate benefits and harms of rehabilitation interventions for non-specific low back pain (LBP) or thoracic spine pain in the pediatric population. METHODS: Seven bibliographic electronic databases were searched from inception to June 16, 2023. Moreover, reference lists of relevant studies and systematic reviews, three targeted websites, and the WHO International Clinical Trials Registry Platform were searched. Paired reviewers independently conducted screening, assessed risk of bias, and extracted data related to study characteristics, methodology, subjects, and results. Certainty of evidence was evaluated based on the GRADE approach. RESULTS: We screened 8461 citations and 307 full-text articles. Ten quantitative studies (i.e., 8 RCTs, 2 non-randomized clinical trials) and one qualitative study were included. With very low to moderate certainty evidence, in adolescents with LBP, spinal manipulation (1-2 sessions/week over 12 weeks, 1 RCT) plus exercise may be associated with a greater likelihood of experiencing clinically important pain reduction versus exercise alone; and group-based exercise over 8 weeks (2 RCTs and 1 non-randomized trial) may reduce pain intensity. The qualitative study found information provided via education/advice and compliance of treatment were related to effective treatment. No economic studies or studies examining thoracic spine pain were identified. CONCLUSIONS: Spinal manipulation and group-based exercise may be beneficial in reducing LBP intensity in adolescents. Education should be provided as part of a care program. The overall evidence is sparse. Methodologically rigorous studies are needed. TRIAL REGISTRATION: CRD42019135009 (PROSPERO).

Effectiveness of postsurgical rehabilitation following lumbar disc herniation surgery: A systematic review.

Introduction: The effectiveness of post-surgical rehabilitation following lumbar disc herniation (LDH) surgery is unclear. Research question: To investigate the effectiveness and safety of rehabilitation interventions initiated within three months post-surgery for adults treated surgically for LDH. Material and methods: This systematic review searched seven databases from inception to November 2023. Independent reviewers screened studies, assessed and extracted data, and rated the certainty of the evidence using the GRADE approach. Results: This systematic review retrieved 20,531 citations and included 25 randomized controlled trials. The high certainty evidence suggests that adding Pilates exercise to routine care and cognitive behavioral therapy may improve function immediately post-intervention (1 RCT), and that adding whole-body magnetic therapy to exercise, pharmacological and aquatic therapy may reduce low back pain intensity (1 RCT) immediately post-intervention. Compared to placebo, pregabalin did not reduce low back pain or leg pain intensity (1 RCT) (moderate to high certainty evidence). We found no differences between: 1) behavioral graded activity vs. physiotherapy (1 RCT); 2) exercise and education vs. neck massage or watchful waiting (1 RCT); 3) exercise, education, and in-hospital usual care vs. in-hospital usual care (1 RCT); 4) functional or staged exercise vs. usual post-surgical care including exercise (2 RCTs); and 5) supervised exercise with education vs. education (1 RCT). No studies assessed adverse events. Discussion and conclusion: Evidence on effective and safe post-surgical rehabilitation interventions is sparse. This review identified two interventions with potential short-term benefits (Pilates exercises, whole-body magnetic therapy) but safety is unclear, and one with an iatrogenic effect (pregabalin).

Systematic Review Procedures for the World Health Organization (WHO) Evidence Syntheses on Benefits and Harms of Structured and Standardized Education/Advice, Structured Exercise Programs, Transcutaneous Electrical Nerve Stimulation (TENS), and Needling Therapies for the Management of Chronic Low Back Pain in Adults.

As commissioned by the WHO, we updated and expanded the scope of four systematic reviews to inform its (in development) clinical practice guideline for the management of CPLBP in adults, including older adults. Methodological details and results of each review are described in the respective articles in this series. In the last article of this series, we discuss methodological considerations, clinical implications and recommendations for future research.

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

PURPOSE: Evaluate benefits and harms of structured exercise programs 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) in electronic databases (inception to 17 May 2022). Eligible RCTs targeted structured exercise programs compared to placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of exercise could be isolated). We extracted outcomes, appraised risk of bias, conducted meta-analyses where appropriate, and assessed certainty of evidence using GRADE. RESULTS: We screened 2503 records (after initial screening through Cochrane RCT Classifier and Cochrane Crowd) and 398 full text RCTs. Thirteen RCTs rated with overall low or unclear risk of bias were synthesized. Assessing individual exercise types (predominantly very low certainty evidence), pain reduction was associated with aerobic exercise and Pilates vs. no intervention, and motor control exercise vs. sham. Improved function was associated with mixed exercise vs. usual care, and Pilates vs. no intervention. Temporary increased minor pain was associated with mixed exercise vs. no intervention, and yoga vs. usual care. Little to no difference was found for other comparisons and outcomes. When pooling exercise types, exercise vs. no intervention probably reduces pain in adults (8 RCTs, SMD = - 0.33, 95% CI - 0.58 to - 0.08) and functional limitations in adults and older adults (8 RCTs, SMD = - 0.31, 95% CI - 0.57 to - 0.05) (moderate certainty evidence). CONCLUSIONS: With moderate certainty, structured exercise programs probably reduce pain and functional limitations in adults and older people with CPLBP.

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.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured and Standardized Education or Advice for Chronic Primary low back pain in Adults.

PURPOSE: Evaluate benefits and harms of education/advice 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 education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. RESULTS: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. CONCLUSION: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty.

Improving Rehabilitation Research to Optimize Care and Outcomes for People with Chronic Primary Low Back Pain: Methodological and Reporting Recommendations from a WHO Systematic Review Series.

Chronic primary low back pain (CPLBP) is a prevalent and disabling condition that often requires rehabilitation interventions to improve function and alleviate pain. This paper aims to advance future research, including systematic reviews and randomized controlled trials (RCTs), on CPLBP management. We provide methodological and reporting recommendations derived from our conducted systematic reviews, offering practical guidance for conducting robust research on the effectiveness of rehabilitation interventions for CPLBP. Our systematic reviews contributed to the development of a WHO clinical guideline for CPLBP. Based on our experience, we have identified methodological issues and recommendations, which are compiled in a comprehensive table and discussed systematically within established frameworks for reporting and critically appraising RCTs. In conclusion, embracing the complexity of CPLBP involves recognizing its multifactorial nature and diverse contexts and planning for varying treatment responses. By embracing this complexity and emphasizing methodological rigor, research in the field can be improved, potentially leading to better care and outcomes for individuals with CPLBP.

Repetitive transcranial magnetic stimulation for chemotherapy-induced peripheral neuropathy in multiple myeloma: A pilot study.

Objective: Chemotherapy-induced peripheral neuropathy is one of the major toxicities in multiple myeloma patients, often resulting in dose reductions or treatment interruptions. Repetitive transcranial magnetic stimulation is a safe non-invasive neuromodulation therapy with potential benefits for chemotherapy-induced peripheral neuropathy. The objective of this study was to investigate the efficacy of repetitive transcranial magnetic stimulation treatment on chemotherapy-induced peripheral neuropathy in multiple myeloma patients. Materials and methods: We screened 30 multiple myeloma patients with chemotherapy-induced peripheral neuropathy who underwent repetitive transcranial magnetic stimulation treatment in this study. Prior to and following repetitive transcranial magnetic stimulation treatment, patients were assessed with nerve conduction velocity, visual analog scale and the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item scale (EORTC QLQ-CIPN20). Categorical and continuous variables were analyzed using Fisher's exact test and Mann-Whitney U test respectively. A p-value < 0.05 (2-tailed) was considered statistically significant. Results: Following repetitive transcranial magnetic stimulation treatment, 24/30 (80.0%) patients reported a reduction in chemotherapy-induced peripheral neuropathy symptoms. Meanwhile, all 15 patients with grade 2 chemotherapy-induced peripheral neuropathy experienced improvements about themselves, compared to 8/10 patient with grade 3 chemotherapy-induced peripheral neuropathy and 1/5 with grade 4 chemotherapy-induced peripheral neuropathy. Visual analog scale scores decreased after repetitive transcranial magnetic stimulation treatment (5.40 ± 1.94 vs 3.10 ± 1.60, p < 0.001). We also observed enhancements in both motor conduction velocity and sensory conduction velocity of patients in bilateral median nerves, posterior tibial nerves, common ulnar nerves and peroneal nerves following repetitive transcranial magnetic stimulation treatment. Analysis of the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item scale data (17.68 ± 8.14 vs 10.50 ± 9.55, p < 0.001) revealed significant reductions in scores. Patients with grade 2-3 (n = 25) exhibited a mean reduction of 8.89 ± 4.24 points, while those with grade 4 (n = 5) showed a difference value of 3.54 ± 3.45, p < 0.001. No adverse events were observed. Conclusion: Our findings suggest that repetitive transcranial magnetic stimulation is a safe and effective therapeutic approach for ameliorating peripheral nerve injury and alleviating the chemotherapy-induced peripheral neuropathy symptoms in multiple myeloma patients. Early initiation of repetitive transcranial magnetic stimulation treatment may yield more favorable outcomes for these patients.

Composite hydrogel based oxidated sodium carboxymethyl cellulose and gelatin loaded carboxymethylated cotton fabric for hemostasis and infected wound treatment.

The fabric-based wound dressings are hard to maintain a moist environment for wound healing while the hemostatic property and gas permeability of some hydrogel-based wound dressings are not ideal. This study first put forward a strategy of checkerboard-pattern wound dressing: 1) preparing the base fabric with hemostatic property, 2) printing multifunctional hydrogels onto one side of the base fabric to form checkerboard patterns, 3) modifying the other side of the base fabric to be hydrophobic. In this manner, the composite dressing not only maintained the advantages of hydrogels, but also inherited good mechanical property, hemostatic property, and gas permeability from the base fabric. Here, the cotton fabric was carboxymethylated to be MCF. To obtain multifunctional hydrogel, sodium carboxymethylcellulose was oxidated to introduce aldehyde groups to form Schiff base with amino groups in gelatin, besides, dopamine and Ag nanoparticles were introduced to endow the hydrogel with antioxidant property and antibacterial activity. The multifunctional hydrogel was printed onto one side of MCF, subsequently, the deposition of paraffin made the other side of this dressing become hydrophobic. The good performance of the obtained dressing in hemostatic process and wound healing demonstrated its potential in the field of wound treatment.

Post-Concussion Symptoms and Disability in Adults With Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Studies investigating long-term symptoms and disability after mild traumatic brain injury (mTBI) have yielded mixed results. This systematic review and meta-analysis aimed to determine the prevalence of self-reported post-concussion symptoms (PCS) and disability following mTBI. We systematically searched MEDLINE, Embase, CINAHL, CENTRAL, and PsycInfo to identify inception cohort studies of adults with mTBI. Paired reviewers independently extracted data and assessed risk of bias with the Scottish Intercollegiate Guidelines Network criteria. We identified 43 eligible studies for the systematic review; 41 were rated as high risk of bias, primarily due to high attrition (> 20%). Twenty-one studies (49%) were included in the meta-analyses (five studies were narratively synthesized; 17 studies were duplicate reports). At 3-6 months post-injury, the estimated prevalence of PCS from random-effects meta-analyses was 31.3% (95% confidence interval [CI] = 25.4-38.4) using a lenient definition of PCS (2-4 mild severity PCS) and 18.3% (95% CI = 13.6-24.0) using a more stringent definition. The estimated prevalence of disability was 54.0% (95% CI = 49.4-58.6) and 29.6% (95% CI = 27.8-31.5) when defined as Glasgow Outcome Scale-Extended <8 and <7, respectively. The prevalence of symptoms similar to PCS was higher in adults with mTBI versus orthopedic injury (prevalence ratio = 1.57, 95% CI = 1.22-2.02). In a meta-regression, attrition rate was the only study-related factor significantly associated with higher estimated prevalence of PCS. Setting attrition to 0%, the estimated prevalence of PCS (lenient definition) was 16.1%. We conclude that nearly one in three adults who present to an emergency department or trauma center with mTBI report at least mild severity PCS 3-6 months later, but controlling for attrition bias, the true prevalence may be one in six. Studies with representative samples and high retention rates are needed.

PD-L1 and the Clinical Outcomes of Ovarian Cancer: Meta-Analysis and Bioinformatical Analysis.

OBJECTIVE: A meta-analysis was performed to analyze the association between PD-L1 expression and overall survival (OS) in various tumors and to identify potential targets through biological information analysis. METHODS: the data were collected from PubMed and Cochrane library, the all analysis of our study were conducted by STATA software and online website. RESULTS: Ten articles (including 11 studies) that met all inclusion criteria were obtained. The combined HR showed that high PD-L1 expression was significantly associated with poor overall survival (HR = 1.84, 95% CI: 1.15-2.93). Pathway analysis revealed that the upregulated genes were primarily involed in biological processes, including nucleic acid transcription, biosynthesis and negative regulation of cell metabolism. The downregulated genes were primarily involed in the regulation of cell cycle, including chromosome separation and DNA metabolism. The top ten genes that were identified were hub genes (CDK1, CCNB1, CCNA2, KIF11, CDC20, UBE2C, NCAPG, AURKA, AURKB, CHEK1), which had significant function in cell differentiation and virus infection. The Kaplan-Meier survival curve indicated that CCNB1, KIF11, UBE2C, NCAPG, AURKA and CHEK1 were statistically significant (P<0.05). CONCLUSION: PD-L1 was found to be a latent biomarker for predicting the prognostic value of cancer and also a therapeutic target.

African swine fever virus M1249L protein antagonizes type I interferon production via suppressing phosphorylation of TBK1 and degrading IRF3.

Cyclic GMP-AMP synthase (cGAS) is a major DNA sensor. The recognition of cytosolic DNA by cGAS triggers a robust innate immune response that restricts the replication of diverse viral pathogens through the type I interferon (IFN) and nuclear factor-κB (NF-κB) pathways. African swine fever virus (ASFV) is a large and complex DNA virus reported to strongly inhibit the cGAS-STING signaling pathway. Herein, 12 ASFV structural proteins were screened to determine their effects on the cGAS-STING pathway. Ectopic expression of the ASFV caspid protein M1249L significantly inhibited the IFN-ß promoter activity induced by the cGAS-STING pathway in a dose-dependent manner. And it could also downregulate the levels of IFN-ß and several interferon-stimulating genes (ISGs) induced by cGAS-STING and 2'3'-cGAMP. Moreover, ASFV M1249L also suppressed phosphorylation of TBK1 by cGAS and STING overexpression. Further study showed that M1249L co-localized and interacted with interferon regulatory factor 3 (IRF3), which led to induce IRF3 degradation by lysosomal pathway. Taken together, our study revealed a novel strategy utilized by ASFV for cGAS-STING-related immune evasion.

Integrating Indigenous healing practices within collaborative care models in primary healthcare in Canada: a rapid scoping review.

OBJECTIVES: In November 2020, a series of reports, In Plain Sight, described widespread Indigenous-specific stereotyping, racism and discrimination limiting access to medical treatment and negatively impacting the health and wellness of Indigenous Peoples in British Columbia, Canada. To address the health inequalities experienced by Indigenous peoples, Indigenous healing practices must be integrated within the delivery of care. This rapid scoping review aimed to identify and synthesise strategies used to integrate Indigenous healing practices within collaborative care models available in community-based primary healthcare, delivered by regulated health professionals in Canada. ELIGIBILITY CRITERIA: We included quantitative, qualitative and mixed-methods studies conducted in community-based primary healthcare practices that used strategies to integrate Indigenous healing practices within collaborative care models. SOURCES OF EVIDENCE: We searched MEDLINE, Embase, Indigenous Studies Portal, Informit Indigenous Collection and Native Health Database for studies published from 2015 to 2021. CHARTING METHODS: Our data extraction used three frameworks to categorise the findings. These frameworks defined elements of integrated healthcare (ie, functional, organisational, normative and professional), culturally appropriate primary healthcare and the extent of community engagement. We narratively summarised the included study characteristics. RESULTS: We identified 2573 citations and included 31 in our review. Thirty-nine per cent of reported strategies used functional integration (n=12), 26% organisational (n=8), 19% normative (n=6) and 16% professional (n=5). Eighteen studies (58%) integrated all characteristics of culturally appropriate Indigenous healing practices into primary healthcare. Twenty-four studies (77%) involved Indigenous leadership or collaboration at each phase of the study and, seven (23%) included consultation only or the level of engagement was unclear. CONCLUSIONS: We found that collaborative and Indigenous-led strategies were more likely to facilitate and implement the integration of Indigenous healing practices. Commonalities across strategies included community engagement, elder support or Indigenous ceremony or traditions. However, we did not evaluate the effectiveness of these strategies.

Reliability and validity of manual palpation for the assessment of patients with low back pain: a systematic and critical review.

BACKGROUND: Static or motion manual palpation of the low back is commonly used to assess pain location and reproduction in low back pain (LBP) patients. The purpose of this study is to review the reliability and validity of manual palpation used for the assessment of LBP in adults. METHOD: We systematically searched five databases from 2000 to 2019. We critically appraised internal validity of studies using QAREL and QUADAS-2 instruments. We stratified results using best-evidence synthesis. Validity studies were classified according to Sackett and Haynes. RESULTS: We identified 2023 eligible articles, of which 14 were low risk of bias. Evidence suggests that reliability of soft tissue structures palpation is inconsistent, and reliability of bony structures and joint mobility palpation is poor. We found preliminary evidence that gluteal muscle palpation for tenderness may be valid in differentiating LBP patients with and without radiculopathy. CONCLUSION: Reliability of manual palpation tests in the assessment of LBP patients varies greatly. This is problematic because these tests are commonly used by manual therapists and clinicians. Little is known about the validity of these tests; therefore, their clinical utility is uncertain. High quality validity studies are needed to inform the clinical use of manual palpation tests.

Effectiveness of non-pharmacological interventions on sleep characteristics among adults with musculoskeletal pain and a comorbid sleep problem: a systematic review.

Sleep problems are common and may be associated with persistent pain. It is unclear whether non-pharmacological interventions improve sleep and pain in adults with comorbid sleep problems and musculoskeletal (MSK) pain. We conducted a systematic review on the effectiveness of non-pharmacological interventions on sleep characteristics among adults with MSK pain and comorbid sleep problems. We searched MEDLINE, EMBASE, CINAHL, Cochrane Central and PsycINFO from inception to April 2, 2021 for randomized controlled trials (RCTs), cohort, and case-control studies. Pairs of independent reviewers critically appraised and extracted data from eligible studies. We synthesized the findings qualitatively. We screened 8459 records and identified two RCTs (six articles, 467 participants). At 9 months, in adults with insomnia and osteoarthritis pain, cognitive behavioral therapy for pain and insomnia (CBT-PI) was effective at improving sleep (Insomnia Severity Index, ISI) when compared to education (OR 2.20, 95% CI 1.25, 3.90) or CBT for pain (CBT-P) (OR 3.21, 95% CI 1.22, 8.43). CBP-P vs. education was effective at increasing sleep efficiency (wrist actigraphy) in a subgroup of participants with severe pain at baseline (mean difference 5.45, 95% CI 1.56, 9.33). At 18 months, CBT-PI, CBT-P and education had similar effectiveness on sleep and pain or health outcomes. In adults with insomnia and knee osteoarthritis, CBT-I improved some sleep outcomes including sleep efficiency (diary) at 3 months (Cohen's d 0.39, 95% CI 0.24, 1.18), and self-reported sleep quality (ISI) at 6 months (Cohen's d - 0.62, 95% CI -1.01, - 0.07). The intervention was no better than placebo (behavioural desensitization) for improving other sleep outcomes related to sleep onset or pain outcomes. Short-term improvement in sleep was associated with pain reduction at 6 months (WOMAC pain subscale) (sensitivity 54.8%, specificity 81.4%). Overall, in two acceptable quality RCTs of adults with OA and comorbid insomnia, CBT-PI/I may improve some sleep outcomes in the short term, but not pain outcomes in the short or long-term. Clinically significant improvements in sleep in the short term may improve longer term pain outcomes. Further high-quality research is needed to evaluate other non-pharmacological interventions for people with comorbid sleep problems and a range of MSK conditions.

Noninvasive management of soft tissue disorders of the shoulder: A clinical practice guideline from the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.

OBJECTIVES: Objective of this study is to develop an evidence-based guideline for the noninvasive management of soft tissue disorders of the shoulder (shoulder pain), excluding major pathology. METHODS: This guideline is based on high-quality evidence from seven systematic reviews. Multidisciplinary experts considered the evidence of effectiveness, safety, cost-effectiveness, societal and ethical values, and patient experiences when formulating recommendations. Target audience is clinicians; target population is adults with shoulder pain. RESULTS: When managing patients with shoulder pain, clinicians should (a) rule out major structural or other pathologies as the cause of shoulder pain and reassure patients about the benign and self-limited nature of most soft tissue shoulder pain; (b) develop a care plan in partnership with the patient; (c) for shoulder pain of any duration, consider low-level laser therapy; multimodal care (heat/cold, joint mobilization, and range of motion exercise); cervicothoracic spine manipulation and mobilization for shoulder pain when associated pain or restricted movement of the cervicothoracic spine; or thoracic spine manipulation; (d) for shoulder pain >3-month duration, consider stretching and/or strengthening exercises; laser acupuncture; or general physician care (information, advice, and pharmacological pain management if necessary); (e) for shoulder pain with calcific tendinitis on imaging, consider shock-wave therapy; (f) for shoulder pain of any duration, do not offer ultrasound; taping; interferential current therapy; diacutaneous fibrolysis; soft tissue massage; or cervicothoracic spine manipulation and mobilization as an adjunct to exercise (i.e., range of motion, strengthening and stretching exercise) for pain between the neck and the elbow at rest or during movement of the arm; (g) for shoulder pain >3-month duration, do not offer shock-wave therapy; and (h) should reassess the patient's status at each visit for worsening of symptoms or new physical, mental, or psychological symptoms, or satisfactory recovery. CONCLUSIONS: Our evidence-based guideline provides recommendations for non-invasive management of shoulder pain. The impact of the guideline in clinical practice requires further evaluation. SIGNIFICANCE: Shoulder pain of any duration can be effectively treated with laser therapy, multimodal care (i.e., heat/cold, joint mobilization, range of motion exercise), or cervicothoracic manipulation and mobilization. Shoulder pain (>3 months) can be effectively treated with exercises, laser acupuncture, or general physician care (information, advice, and pharmacological pain management if necessary).

Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, In Vitro and In Vivo Investigations of Jamunones.

Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.