WITHDRAWN: Use of proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) receiving dual-antiplatelet therapy (DAPT).

 : This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been withdrawn at the request of the authors, editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease.

Mitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and the lack of effective therapies. Environmental exposures, such bacterial and viral infection, can further compromise mitochondrial function and exacerbate the progression of MtD. Infections in MtD patients more frequently progress to sepsis, pneumonia, and other detrimental inflammatory endpoints. However, the underlying immune alterations that enhance immunopathology in MtD remain unclear, constituting a key gap in knowledge that complicates treatment and increases mortality in this population. Here we employ in vitro and in vivo approaches to clarify the molecular and cellular basis for innate immune hyperactivity in models of polymerase gamma (Polg)-related MtD. We reveal that type I interferon (IFN-I)-mediated upregulation of caspase-11 and guanylate-binding proteins (GBPs) increase macrophage sensing of the opportunistic microbe Pseudomonas aeruginosa (PA) in Polg mutant mice. Furthermore, we show that excessive macrophage cytokine secretion and pyroptotic cell death contribute to lung inflammation and morbidity after infection with PA. Our work sheds new light on innate immune dysregulation in MtD and reveals potential targets for limiting infection- and inflammation-related complications in Polg-related MtD.

Prevalence and characteristics of healthcare utilization with different providers among Canadians with chronic back problems: A population-based study.

Introduction: Understanding healthcare utilization by Canadians with back problems informs healthcare planning nationally. Research question: What is the prevalence of utilization of healthcare providers (medical doctors, chiropractors, physiotherapists, nurses), and associated characteristics among Canadians with chronic back problems (2001-2016)? Material and methods: This population-based study used Canadian Community Health Survey data (2001-2016) restricted to respondents with chronic back problems (aged ≥12 years). We used self-reported consultation with healthcare providers (medical doctors, chiropractors, physiotherapists, nurses) from 2001-2010, and self-reported regular healthcare provider from 2015-2016. We calculated the 12-month prevalence of utilization with providers, and used modified Poisson regression to assess sociodemographic, health-related and behavioural factors associated with utilization of different providers. Results: From 2001 to 2010 and 2015/2016, respectively, prevalence of utilization of medical doctors was 87.9% (95% CI 87.6-88.2) and 86.7% (95% CI 85.9-87.5); chiropractors 24.0% (95% CI 23.6-24.4) and 14.5% (95% CI 13.8-15.3); physiotherapists 17.2% (95% CI 16.9-17.6) and 10.7% (95% CI 10.0-11.4); nurses 14.0% (95% CI 13.7-14.2) and 6.6% (95% CI 6.1-7.0). Females were more likely to see any provider than males. Persons of lower socioeconomic status were less likely to consult chiropractors or physiotherapists (2001-2016), or nurses (2001-2010). Immigrants were less likely to consult chiropractors or nurses. Persons aged >65 years were less likely to consult chiropractors or physiotherapists, and those with fair/poor general health were less likely to consult chiropractors, but more likely to consult other providers. Discussion and conclusion: Medical doctors were most commonly consulted by Canadians with back problems, then chiropractors and physiotherapists. Characteristics of healthcare utilization varied by provider. Findings inform the need to strengthen healthcare delivery for Canadians with back problems.

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).

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).

NCCN Guidelines® Insights: Prostate Cancer, Version 3.2024.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.

Characterizing high-cost healthcare users among adults with back pain in Ontario, Canada: a population-based cohort study.

ABSTRACT: Some patients with back pain contribute disproportionately to high healthcare costs; however, characteristics of high-cost users with back pain are not well defined. We described high-cost healthcare users based on total costs among a population-based cohort of adults with back pain within the Ontario government's single-payer health system across sociodemographic, health, and behavioural characteristics. We conducted a population-based cohort study of Ontario adult (aged 18 years or older) respondents of the Canadian Community Health Survey (CCHS) with back pain (2003-2012), linked to administrative data (n = 36,605; weighted n = 2,076,937, representative of Ontario). Respondents were ranked based on gradients of total healthcare costs (top 1%, top 2%-5%, top 6%-50%, and bottom 50%) for 1 year following the CCHS survey, with high-cost users as top 5%. We used multinomial logistic regression to investigate characteristics associated with the 4 cost groups. Top 5% of cost users accounted for 49% ($4 billion CAD) of total healthcare spending, with inpatient hospital care as the largest contributing service type (approximately 40% of costs). Top 5% high-cost users were more likely aged 65 years or older (ORtop1% = 16.6; ORtop2-5% = 44.2), with lower income (ORtop1% = 3.6; ORtop 2-5% = 1.8), chronic disease(s) (ORtop1% = 3.8; ORtop2-5% = 1.6), Aggregated Diagnosis Groups measuring comorbidities (ORtop1% = 25.4; ORtop2-5% = 13.9), and fair/poor self-rated general health (ORtop1% = 6.7; ORtop2-5% = 4.6) compared with bottom 50% users. High-cost users tended to be current/former smokers, obese, and report fair/poor mental health. High-cost users (based on total costs) among adults with back pain account for nearly half of all healthcare spending over a 1-year period and are associated with older age, lower income, comorbidities, and fair/poor general health. Findings identify characteristics associated with a high-risk group for back pain to inform healthcare and public health strategies that target upstream determinants.

Association of COVID-19 vaccination with duration of hospitalization in older adults in Hong Kong.

INTRODUCTION: The association between COVID-19 vaccination and length of hospital stay may provide further insight into vaccination benefits, but few studies have investigated such associations in detail. We aimed to investigate the association between COVID-19 vaccination and length of hospital stay in COVID-19 patients during Omicron waves in Hong Kong, and explore potential predictors. METHODS: This retrospective cohort study was conducted on local patients aged ≥60 years who were admitted due to COVID-19 infection in Hong Kong in 2022, from 1 February to 22 November, and with 28 days of follow-up since admission. The exposure was either not vaccinated; or having received 2/3/4 doses of CoronaVac (Sinovac); or 2/3/4 doses of BNT162b2 (BioNTech/Fosun Pharma/Pfizer). Length of stay in hospital was the main outcome. Accelerated failure time models were used to quantify variation in hospital stay for vaccinated compared with unvaccinated patients, accounting for age, sex, comorbidity, type of vaccine and number of doses received, care home residence and admission timing; stratified by age groups and epidemic waves. RESULTS: This study included 32,398 patients aged 60 years and above for main analysis, their median (IQR) age was 79 (71-87) years, 53% were men, and 40% were unvaccinated. The patients were stratified by confirmation prior to or since 23 May 2022, resulting in a sample size of 15,803 and 16,595 in those two waves respectively. Vaccinated patients were found to have 13-39% shorter hospital stay compared to unvaccinated patients. More vaccine doses received were associated with shorter hospital stay, and BNT162b2 recipients had slightly shorter hospital stays than CoronaVac recipients. CONCLUSION: Vaccination was associated with reduced hospital stay in breakthrough infections. Increased vaccination uptake in older adults may improve hospital bed turnover and public health outcomes especially during large community epidemics.

Introduction to target trial emulation in rehabilitation: a systematic approach to emulate a randomized controlled trial using observational data.

Rehabilitation providers and policymakers need valid evidence to make informed decisions about the healthcare needs of the population. Whenever possible, these decisions should be informed by randomized controlled trials (RCTs). However, there are circumstances when evidence needs to be generated rapidly, or when RCTs are not ethical or feasible. These situations apply to studying the effects of complex interventions, including rehabilitation as defined by Cochrane Rehabilitation. Therefore, we explore using the target trial emulation framework by Hernán and colleagues to obtain valid estimates of the causal effects of rehabilitation when RCTs cannot be conducted. Target trial emulation is a framework guiding the design and analysis of non-randomized comparative effectiveness studies using observational data, by emulating a hypothetical RCT. In the context of rehabilitation, we outline steps for applying the target trial emulation framework using real world data, highlighting methodological considerations, limitations, potential mitigating strategies, and causal inference and counterfactual theory as foundational principles to estimating causal effects. Overall, we aim to strengthen methodological approaches used to estimate causal effects of rehabilitation when RCTs cannot be conducted.

Pulsed low-dose-rate radiation (PLDR) reduces the tumor-promoting responses induced by conventional chemoradiation in pancreatic cancer-associated fibroblasts.

Pancreatic cancer is becoming increasingly deadly, with treatment options limited due to, among others, the complex tumor microenvironment (TME). This short communications study investigates pulsed low-dose-rate radiation (PLDR) as a potential alternative to conventional radiotherapy for pancreatic cancer neoadjuvant treatment. Our ex vivo research demonstrates that PLDR, in combination with chemotherapy, promotes a shift from tumor-promoting to tumor-suppressing properties in a key component of the pancreatic cancer microenvironment we called CAFu (cancer-associated fibroblasts and selfgenerated extracellular matrix functional units). This beneficial effect translates to reduced desmoplasia (fibrous tumor expansion) and suggests PLDR's potential to improve total neoadjuvant therapy effectiveness. To comprehensively assess this functional shift, we developed the HOST-Factor, a single score integrating multiple biomarkers. This tool provides a more accurate picture of CAFu function compared to individual biomarkers and could be valuable for guiding and monitoring future therapeutic strategies. Our findings support the ongoing NCT04452357 clinical trial testing PLDR safety and TME normalization potential in pancreatic cancer patients. The HOST-Factor will be used in samples collected from this trial to validate its potential as a key tool for personalized medicine in this aggressive disease.

Prevalence of Unmet Rehabilitation Needs Among Canadians Living With Long-term Conditions or Disabilities During the First Wave of the COVID-19 Pandemic.

OBJECTIVE: We aimed to describe the prevalence of unmet rehabilitation needs among a sample of Canadians living with long-term conditions or disabilities during the first wave of the COVID-19 pandemic. DESIGN: Cross-sectional survey. SETTING: Individuals residing in Canada during the first wave of the COVID-19 pandemic. PARTICIPANTS: Eligible participants were Canadians living with long-term conditions or disabilities, 15 years or older living in 1 of the 10 provinces or 3 territories (n=13,487). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: We defined unmet rehabilitation needs as those who reported needing rehabilitation (ie, physiotherapy/massage therapy/chiropractic, speech, or occupational therapy, counseling services, support groups) but did not receive it because of the COVID-19 pandemic. We calculated the national, age, gender, and province/territory-specific prevalence and 95% confidence interval of unmet rehabilitation needs. RESULTS: During the first wave of the pandemic, the prevalence of unmet rehabilitation needs among Canadians with long-term conditions or disabilities was 49.3% (95% confidence interval [CI]; 48.3, 50.3]). The age-specific prevalence was higher among individuals 15-49 years old (55.6%; 95% CI [54.2, 57.1]) than those 50 years and older (46.0%; 95% CI [44.5, 47.4]). Females (53.7%; 95% CI [52.6, 54.9]) had higher unmet needs than males (44.1%; 95% CI [42.3, 45.9]). Unmet rehabilitation needs varied across provinces and territories. CONCLUSIONS: In this sample, almost 50% of Canadians living with long-term conditions or disabilities had unmet rehabilitation needs during the first wave of the COVID-19 pandemic. This suggests that a significant gap between the needs for and delivery of rehabilitation care existed during the early phase of the pandemic.

Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study.

Background: Hong Kong contained COVID-19 for two years but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. We reflected on pandemic preparedness and responses by assessing COVID-19 transmission and associated disease burden in the context of implementation of various public health and social measures (PHSMs). Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing the temporal changes non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults ≥65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic. Funding: Health and Medical Research Fund.

A pooled patient-reported outcomes analysis of moderately hypofractionated proton beam therapy and photon-based intensity modulated radiation therapy for low- or intermediate-risk prostate cancer.

BACKGROUND: We sought to characterize and compare late patient-reported outcomes (PROs) after moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) for localized prostate cancer (PC). METHODS: This multi-institutional analysis included low- or intermediate-risk group PC patients treated with moderately hypofractionated radiation to an intact prostate stratified by treatment modality: IMRT or PBT. The primary outcomes were prospectively collected patient-reported late gastrointestinal (GI) and genitourinary (GU) toxicity assessed by International Prostate Symptom Score (IPSS) and Expanded PC Index Composite (EPIC). Multivariable regression analysis (MVA) controlling for age, race, and risk group tested the effect of time, treatment, and their interaction. RESULTS: 287 IMRT and 485 PBT patients were included. Intermediate risk group (81.2 vs. 68.2%; p < 0.001) and median age at diagnosis (70 vs. 67 years; p < 0.001) were higher in the IMRT group. On MVA, there was no significant difference between modalities. PBT IPSS did not differ from IMRT IPSS at 12 months (odds ratio [OR], 1.19; p = 0.08) or 24 months (OR, 0.99; p = 0.94). PBT EPIC overall GI function at 12 months (OR, 3.68; p = 0.085) and 24 months (OR 2.78; p = 0.26) did not differ from IMRT EPIC overall GI function. At 24 months, urinary frequency was no different between PBT and IMRT groups (OR 0.35; p = 0.096). CONCLUSIONS: This multi-institutional analysis of low- or intermediate-risk PC treated with moderately hypofractionated PBT and IMRT demonstrated low rates of late patient-reported GI and GU toxicities. After covariate adjustment, late GI and GU PROs were not significantly different between PBT or IMRT cohorts.

Characteristics of Canadians Living With Long-Term Health Conditions or Disabilities Who Had Unmet Rehabilitation Needs During the First Wave of the COVID-19 Pandemic: A Cross-sectional Study.

OBJECTIVE: This study aimed to describe the characteristics associated with unmet rehabilitation needs in a sample of Canadians with long-term health conditions or disabilities during the first wave of the COVID-19 pandemic. DESIGN: We used data from the Impacts of COVID-19 on Canadians Living With Long-Term Conditions and Disabilities, a national cross-sectional survey with 13,487 respondents. Unmet needs were defined as needing rehabilitation (ie, physiotherapy/massage/chiropractic, speech therapy, occupational therapy, counseling services, or support groups) but not receiving due to the pandemic. We used multivariable modified Poisson regression to examine the association between demographic, socioeconomic, and health-related characteristics and unmet rehabilitation needs. RESULTS: More than half of the sample were 50 years and older (52.3%), female (53.8%), and 49.3% reported unmet rehabilitation needs. Those more likely to report unmet needs were females, those with lower socioeconomic status (receiving disability benefits or social assistance, job loss, increased work hours, decreased household income or earnings), and those with lower perceived general health or mental health status. CONCLUSIONS: Among Canadians with disabilities or chronic health conditions, marginalized groups are more likely to report unmet rehabilitation needs. Understanding the systemic and upstream determinants is necessary to develop strategies to minimize unmet rehabilitation needs and facilitate the delivery of equitable rehabilitation services.

Minimal important difference of the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in persons with chronic low back pain.

BACKGROUND: The World Health Organization Disability Assessment Schedule 2.0 12-item survey (WHODAS-12) is a questionnaire developed by the WHO to measure functioning across health conditions, cultures, and settings. WHODAS-12 consists of a subset of the 36 items of WHODAS-2.0 36-item questionnaire. Little is known about the minimal important difference (MID) of WHODAS-12 in persons with chronic low back pain (LBP), which would be useful to determine whether rehabilitation improves functioning to an extent that is meaningful for people experiencing the condition. Our objective was to estimate an anchor-based MID for WHODAS-12 questionnaire in persons with chronic LBP. METHODS: We analyzed data from two cohort studies (identified in our previous systematic review) conducted in Europe that measured functioning using the WHODAS-36 in adults with chronic LBP. Eligible participants were adults with chronic LBP with scores on another measure as an anchor to indicate participants with small but important changes in functioning over time [Short-form-36 Physical Functioning (SF36-PF) or Oswestry Disability Index (ODI)] at baseline and follow-up (study 1: 3-months post-treatment; study 2: 1-month post-discharge from hospital). WHODAS-12 scores were constructed as sums of the 12 items (scored 0-4), with possible scores ranging from 0 to 48. We calculated the mean WHODAS-12 score in participants who achieved a small but meaningful improvement on SF36-PF or ODI at follow-up. A meaningful improvement was an MID of 4-16 on ODI or 5-16 on SF36-PF. RESULTS: Of 70 eligible participants in study 1 (mean age = 54.1 years, SD = 14.7; 69% female), 18 achieved a small meaningful improvement based on SF-36 PF. Corresponding mean WHODAS-12 change score was - 3.22/48 (95% CI -4.79 to -1.64). Of 89 eligible participants in study 2 (mean age = 65.5 years, SD = 11.5; 61% female), 50 achieved a small meaningful improvement based on ODI. Corresponding mean WHODAS-12 change score was - 5.99/48 (95% CI - 7.20 to -4.79). CONCLUSIONS: Using an anchor-based approach, the MID of WHODAS-12 is estimated at -3.22 (95% CI -4.79 to -1.64) or -5.99 (95% CI - 7.20 to -4.79) in adults with chronic LBP. These MID values inform the utility of WHODAS-12 in measuring functioning to determine whether rehabilitation or other health services achieve a minimal difference that is meaningful to patients with chronic LBP.

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.