Efficacy and Safety of Medicines Targeting Neurotrophic Factors in the Management of Low Back Pain: Protocol for a Systematic Review and Meta-Analysis (Preprint)

BACKGROUND Low back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of nonspecific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF inhibitors have been tested in some randomized controlled trials (RCTs) in recent years, showing promise for the treatment of chronic LBP; however, their efficacy and safety need to be evaluated to guide regulatory actions. OBJECTIVE The aim of this study is to evaluate the efficacy and safety of medicines targeting neurotrophins in patients with LBP and sciatica. METHODS In this systematic review, we will include published and unpublished records of parallel RCTs and the first phase of crossover RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search the CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Registry Platform databases from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report sufficient data and compare the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration tool, and form judgments of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct subgroup analyses by condition, type of medication, and time point. We will also assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be included in the meta-analysis will be reported narratively. RESULTS The protocol was registered on the Open Science Framework on May 19, 2020. As of December 2020, we have identified 1932 records. CONCLUSIONS This systematic review and meta-analysis will assess the evidence for the efficacy and safety of NGF inhibitors for pain in patients with nonspecific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica. CLINICALTRIAL Open Science Framework; https://osf.io/b8adn/ INTERNATIONAL REGISTERED REPORT DERR1-10.2196/22905 </sec

Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain : systematic review and meta-analysis

Abstract: Objective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection: Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis: Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results: 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference -7.7, 95% confidence interval-12.1 to-3.3) but not a reduction in disability (-3.3, -7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions: Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/

Data Informing Governing Body Resistance-Training Guidelines Exhibit Sex Bias: An Audit-Based Review

The objective of this review was to examine the ratio of female and male participants utilised in data informing consensus statements and position stands in the field of resistance training (RT). In order to achieve this objective, we conducted an ‘audit’ style review. We accessed three databases: SPORTDiscus, MEDLINE and Google Scholar utilising the following search terms: resistance or strength training AND consensus statements or position statements/stands. Eligibility criteria included consensus statements and position stands for RT in youth, adults and older adults. In this paper we have used the term ‘female’ to describe biological sex. Gender is a social construct and often describes roles and behaviours that society assigns to men or women. In this paper we have used the term ‘women’ to describe gender. Reference lists from each guideline were screened with the number of male and female participants extracted from each study. We also extracted data on the gender of the authors of the statements. We located 11 guidelines encompassing a total of 104,251,363 participants. Youth guidelines were comprised of 69% male participants. There were 287 studies that included both sexes, 205 male-only and 92 female-only studies. Adult guidelines were comprised of 70% male participants. There were 104 studies that included both sexes, 240 male-only and 44 female-only studies. Older adult guidelines were comprised of 54% female participants. There were 395 studies that included both sexes, 112 male-only and 83 female-only studies. Women authors comprised 13% of all authors of position stands and consensus statements. These results demonstrate an under-representation of females and women as both participants and as authors. It is imperative to ensure that data informing governing body guidelines and consensus statements are representative of the population they aim to inform. If this is not possible, guidelines should clearly state when their data and recommendations are based primarily upon one sex

The effectiveness and safety of isometric resistance training for adults with high blood pressure: a systematic review and meta-analysis

High blood pressure (BP) is a global health challenge. Isometric resistance training (IRT) has demonstrated antihypertensive effects, but safety data are not available, thereby limiting its recommendation for clinical use. We conducted a systematic review of randomized controlled trials comparing IRT to controls in adults with elevated BP (systolic ≥130 mmHg/diastolic ≥85 mmHg). This review provides an update to office BP estimations and is the first to investigate 24-h ambulatory BP, central BP, and safety. Data were analyzed using a random-effects meta-analysis. We assessed the risk of bias with the Cochrane risk of bias tool and the quality of evidence with GRADE. Twenty-four trials were included (n = 1143; age = 56 ± 9 years, 56% female). IRT resulted in clinically meaningful reductions in office systolic (-6.97 mmHg, 95% CI -8.77 to -5.18, p p p = 0.02) but not 24-h systolic BP (-2.77 mmHg, 95% CI -6.80 to 1.25, p = 0.18). These results are very low/low certainty with high heterogeneity. There was no significant increase in the risk of IRT, risk ratio (1.12, 95% CI 0.47 to 2.68, p = 0.8), or the risk difference (1.02, 95% CI 1.00 to 1.03, p = 0.13). This means that there is one adverse event per 38,444 bouts of IRT. IRT appears safe and may cause clinically relevant reductions in BP (office, central BP, and 24-h diastolic). High-quality trials are required to improve confidence in these findings. PROSPERO (CRD42020201888); OSF (https://doi.org/10.17605/OSF.IO/H58BZ)

Digital Physical Activity and Exercise Interventions for People Living with Chronic Kidney Disease: A Systematic Review of Health Outcomes and Feasibility

Physical activity is essential to interrupt the cycle of deconditioning associated with chronic kidney disease (CKD). However, access to targeted physical activity interventions remain under-supported due to limited funding and specialised staff. Digital interventions may address some of these factors. This systematic review sought to examine the evidence base of digital interventions focused on promoting physical activity or exercise and their effect on health outcomes for people living with CKD. Electronic databases (PubMed, CINAHL, Embase, Cochrane) were searched from 1 January 2000 to 1 December 2023. Interventions (smartphone applications, activity trackers, websites) for adults with CKD (any stage, including transplant) which promoted physical activity or exercise were included. Study quality was assessed, and a narrative synthesis was conducted. Of the 4057 records identified, eight studies (five randomised controlled trials, three single-arm studies) were included, comprising 550 participants. Duration ranged from 12-weeks to 1-year. The findings indicated acceptability and feasibility were high, with small cohort numbers and high risk of bias. There were inconsistent measures of physical activity levels, self-efficacy, body composition, physical function, and psychological outcomes which resulted in no apparent effects of digital interventions on these domains. Data were insufficient for meta-analysis. The evidence for digital interventions to promote physical activity and exercise for people living with CKD is limited. Despite popularity, there is little evidence that current digital interventions yield the effects expected from traditional face-to-face interventions. However, 14 registered trials were identified which may strengthen the evidence-base