Abstract

Background
Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control.

Methods/design
The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) ​≥ ​30 ​kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention.

Discussion
This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA.

Backgrounds

Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities [1]. Its increased prevalence and severity make it burdensome for people afflicted with the disease, and for health care organizations intended to administer care [2]. Obesity and OA were first linked in 1945 and this relationship has since been verified repeatedly [[3], [4], [5], [6]]. Obesity is a major risk factor associated with knee pain; people with obesity were 2.7 times more likely to have knee OA than adults without obesity [7].

Our mechanistic model, influenced by the seminal work of Griffin and Guilak [8], supports the premise that dietary weight loss and exercise may reduce knee joint loads, lower inflammation, and increase self-efficacy resulting in a lower incidence of structural knee OA (Fig. 1). Previous work showed that weight loss decreased knee joint loads such that every pound lost was associated with a 4-pound reduction in knee compressive forces while walking. The cumulative effect of this load reduction, over thousands of steps per day, reduces microdamage to the subchondral plate and calcified cartilage [9]. These areas are close to the overlying articular cartilage and likely protect articular cartilage integrity (Fig. 1).

Discussion

Implementing a randomized clinical trial designed to prevent incident knee OA presents numerous challenges. OA disease status and severity are defined structurally via x-ray [36] or MRI [19] and clinically using a combination of symptoms reported by the patient and derived from a physical exam [66]. The primary outcome measure for TOPS is structural knee OA using MRI, due to its superior sensitivity and granularity compared to radiographic assessments. In addition, the use of radiographic assessments as the primary outcome measure to determine the presence or absence of incident knee OA would have increased the sample size by 478 participants (39 ​%), requiring additional clinical centers and greater costs to test the hypothesis effectively.

Losing weight and preventing weight regain are difficult [67]. Biological changes fight attempts to maintain weight loss; the body acts in starvation mode increasing feelings of hunger, satiety is suppressed, metabolic rate slows, all in an attempt to defend higher body weights [68]. Psychosocial obstacles include decreased self-efficacy, increased chronic perceived psychosocial stress, and using food for comfort; environmental obstacles include large food portions and food availability [69]. Our previous work provides encouragement that most of the weight-loss attained by the TOPS diet and exercise group can be retained long-term with implementation of the weight-loss maintenance program. In a subsample of the IDEA cohort (N ​= ​94), the diet-only group retained 5.8 ​kg (65 ​%) of an 8.9 ​kg weight loss 3.5 years following completion of the 18-month diet intervention [70]. Maintenance of this clinically important weight-loss occurred without any post-intervention interaction with the study staff.

Abstract

To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function. In rats treated with canagliflozin combined with aerobic exercise, the expression of cytochrome P450 (CYP) 4A3, CYP4A8, COL1A1, COL3A1, and FN1 was reduced, while the expression of CYP26B1, ALDH1A2, and CYP1A1 increased significantly. Additionally, canagliflozin combined with aerobic exercise decreased the phosphorylation of AKT and ERK1/2. Canagliflozin combined with aerobic exercise has a positive effect on the development of CHF via the regulation of retinol metabolism and the AKT/ERK signaling pathway.

Introduction

Chronic heart failure (CHF), the most prevalent form of cardiovascular illness, is a global health issue with a high death and morbidity rate.1 The disease affects about 2% of the adult population worldwide, and the 5-year mortality rate is estimated to be between 45 and 60%.2 CHF is a complex condition characterized by a cardiac muscle’s inability to maintain blood supply to peripheral tissues, resulting in decreased systemic energy metabolism.3 Multiple studies have demonstrated that regulating cardiac energy metabolism is critical for treatment.4,5 The β-oxidation of fatty acids in the mitochondria satisfies the heart’s high energy requirements. Oliveros et al. observed previously observed that a vitamin A deficit paired antioxidant defenses, promoted lipid peroxidation in the adult rat heart, and altered aortic lipid metabolism.6 The peroxisome proliferator-activated receptor (PPAR) is a ligand-activated nuclear transcription factor.7 PPAR modulates fatty acid oxidation (FAO) and mitochondrial bioenergetics, suppresses myocardial remodeling and fibrosis, and improves HF.8 Consequently, we must investigate new techniques for enhancing cardiac function by ameliorating abnormalities of cardiac energy metabolism, preventing cardiac remodeling and fibrosis, and thereby preventing or postponing the advancement of heart failure.

Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT-2), has been demonstrated to benefit HF with a lower ejection fraction.9 SGLT-2 inhibitors (canagliflozin, and so forth) for patients with CHF, improve the quality of life, and reduce mortality, morbidity, and readmission rates.10 In diabetic and nondiabetic subjects, canagliflozin treatment significantly reduced the risk of cardiovascular death, myocardial infarction, and hospitalization for hypertension.11 In addition, SGLT-2 inhibitors can improve fatty acid metabolism and utilize ketone bodies to create mitochondrial energy, so enhancing the aerobic metabolism of skeletal muscle, inhibiting anaerobic metabolism, and enhancing aerobic exercise capacity.12 Canagliflozin has been demonstrated to decrease myocardial glucose metabolism, enhance myocardial fatty acid metabolism, and increase the circulation of ketone bodies,13 thereby ameliorating heart failure via modifying myocardial energy metabolism and oxidative stress.14

Results

Canagliflozin combined with aerobic exercise improved isoproterenol-induced cardiac dysfunction
To investigate the effect of canagliflozin combined with aerobic exercise on CHF, cardiac function was assessed using echocardiography. After 10 days of ISO administration, the levels of LVEF (p < 0.001) and LVFS (p < 0.001) in the ISO group were significantly lower than in the control group, indicating that the CHF rat model was successfully established. LVEF and LVFS levels were significantly higher in the ISO+CA group (LVEF, p < 0.05; LVFS, p < 0.05), the ISO+AE group (LVEF, p < 0.05; LVFS, p < 0.05), and the ISO+AE+CA group (LVEF, p < 0.01; LVFS, p < 0.01). Moreover, compared to the ISO group, the levels of LVIDs (p < 0.05) and LVESV (p < 0.05) were significantly reduced in the ISO+AE+CA group but not in the ISO+CA group (LVIDs, p = 0.21; LVESV, p = 0.21). (Figures 1A and 1B, Table 1).

Abstract

Introduction
Sport-related concussions (SRC) have been a concern in all sports, including soccer. The long-term effects of soccer-related head injuries are a public health concern. The Concussion in Sport Group (CISG) released a consensus statement in 2017 and several soccer governing associations have published their own SRC guidelines while referring to it but it is unclear whether this has been universally adopted.

Research question
We aimed to investigate whether guidelines published by soccer associations have any discrepancies; and the extent to which they follow the CISG recommendations.

Materials and methods
A scoping review of available soccer-specific SRC guidelines was performed via databases PubMed, Google Scholar, and official soccer association websites via web browser Google. The inclusion criteria were soccer-specific SRC guidelines. Comparisons between guidelines were made concerning the following index items: initial (on-site) assessment, removal from play, re-evaluation with neuroimaging, return-to-sport protocol, special populations, and education.

Results
Nine soccer associations with available guidelines were included in this review. Guidelines obtained were from official associations in the United Kingdom, United States of America, Canada, Australia, and New Zealand. When compared to each other and the CISG recommendations, discrepancies were found within guidelines regarding the index items. Additionally, major soccer associations in some countries famous for soccer were found to have not published any publicly available guidelines.

Discussion and conclusion
SRC guidelines from different soccer associations contain discrepancies which may be detrimental to athletes, both short and long-term. We recommend that all major soccer governing associations publish guidelines that are standardised and accessible to all athletes.

Introduction

A concussion can be defined as a transient and sudden alteration of consciousness following traumatic biomechanical forces transmitted to the brain either directly or indirectly (Khurana and Kaye, 2012). Sport-related concussion (SRC) has been a growing concern over several years and has been attracting further attention amongst athletes and healthcare professionals due to recently publicised effects on both their immediate and long-term neurological health. Soccer is a sport with high concussion rates in comparison with others (Pierpoint and Collins, 2021). The injury rates amongst athletes of the National Collegiate Athletic Association (NCAA) being 0.28 and 0.41 per 1000 game exposures for male and female soccer athletes respectively. This is in comparison with other contact sports such as men’s wrestling (0.25), American football (0.37), basketball (0.16), ice hockey (0.41); and women’s basketball (0.22), gymnastics (0.16), and field hockey (0.18) (Hootman et al., 2007). High concussion rates were also seen in a 2020 study by Vedung et al., where the concussion incidence was 1.19 per 1000 game hours (Vedung et al., 2020).

Recent evidence from 2019 (Scotland) and 2023 (Sweden) showed that former elite soccer players are more likely to die from neurogenerative disease, which was attributed to the frequency of concussions and repetitive heading during their playing days (Mackay et al., 2019; Ueda et al., 2023). There has also been coverage from mainstream media reporting on former athletes that have developed neurodegenerative disease after sustaining SRC’s during their playing careers. For example, in an article from 2020, forty ex-soccer players were reported to take legal action against the English Football Association for dementia-related negligence due to brain injuries sustained (PA Media, 2020). Increasing attention has therefore been brought to this issue, which has raised questions on the effectiveness and utilisation of concussion protocols currently in place.

Conclusion

This scoping review identified discrepancies between soccer-specific SRC guidelines published by different official bodies. The major discrepancies identified were found in the timeframes for the return-to-sport protocol; the time recommended for the initial rest phase; and the decision to allow same day return-to-play after a suspected concussion. Possible implications of these discrepancies are that athletes could be managed in vastly different ways without any clarity on which guidelines would be best. This could lead to outcomes where, for example, athletes could be rested for too long or the opposite where athletes could be rushed back into play prematurely. Furthermore, the discrepancies could be putting certain populations at a higher risk of subsequently poorer neurocognitive outcomes after sustaining a concussion; for example, amateur athletes that do not have access to facilities like an individualised management plan with close monitoring of their progression through the different steps of the return-to-sport protocol. Due to the lack of studies in this area, it is unclear whether these discrepancies are detrimental to athletes and whether they may pose a risk, both at short-and long term. Soccer is one of the most popular sports in the world and SRCs continue to be a relevant issue. This is a field of growing interest amongst healthcare professionals and considerations for additional specific information about risk prevention and the use of neuroimaging should be made to include them within future guidelines.

It is fortunate that the most recent update from the CISG was concluded with the 6th International Conference on Concussion in Sport, held in 2022 (Patricios et al., 2023). This consensus statement was only just published in June 2023 and includes updated strategies for return-to-sport and material such as the Sport Concussion Assessment Tool-6 (SCAT-6), the Child SCAT-6, the Concussion Recognition Tool-6 (CRT-6), the Sport Concussion Office Assessment Tool-6 (SCOAT-6), and the Child SCOAT-6. These updates provide a fresh opportunity for soccer associations to update their guidelines in a consistent and collaborative manner.

Abstract

Background
High blood pressure (BP) is a major contributor to mortality and cardiovascular diseases. Despite the known benefits of exercise for reducing BP, it is crucial to identify the most effective physical activity (PA) intervention. This systematic review and network meta-analysis (NMA) aimed to evaluate the available evidence on the effectiveness of various PA interventions for reducing BP and to determine their hierarchy based on their impact on BP.

Methods
A search of PubMed, SPORTDiscus, PsycINFO, Web of Science, CINAHL, Cochrane, and Eric databases was conducted up to December 2022 for this systematic review and NMA. Randomized controlled trials and quasi-experimental studies targeting healthy children and adolescents aged 6–12 years old were included in this study. Only studies that compared controlled and intervention groups using PA or exercise as the major influence were included. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three independent investigators performed the literature screening, data extraction, and risk of bias assessment. We used Bayesian arm-based NMA to synthesize the data. The primary outcomes were systolic BP and diastolic BP. We calculated the mean differences (MDs) in systolic BP and diastolic BP before and after treatment. Mean treatment differences were estimated using NMA and random-effect models.

Results
We synthesized 27 studies involving 15,220 children and adolescents. PA combined with nutrition and behavior change was the most effective intervention for reducing both systolic BP and diastolic BP ((MD: –8.64, 95% credible interval (95%CI):–11.44 to –5.84); (MD: –6.75, 95%CI: –10.44 to –3.11)), followed by interventions with multiple components ((MD: –1.39, 95%CI: –1.94 to –0.84); (MD: –2.54, 95%CI: –4.89 to –0.29)).

Conclusion
Our findings suggest that PA interventions incorporating nutrition and behavior change, followed by interventions with multiple components, are most effective for reducing both systolic blood pressure and diastolic blood pressure in children and adolescents.

Introduction

High blood pressure (HBP), or hypertension, occurs when the blood exerts too much pressure against the walls of blood vessels due to systolic and diastolic forces.1 It is a significant risk factor for cardiovascular diseases, contributing to 10.1 million deaths and 208.1 million cases of overall disease burden worldwide in the past 2 decades.2 The death rate attributable to HBP increased to 34.2% between 2009 and 2019,3, 4, 5 with hypertension projected to affect 41% of US adults by 2030.6,7 The economic burden of hypertension is expected to rise significantly, with direct costs projected to triple to USD 389.9 billion and indirect costs to double to USD 42 billion by 2030.6,8,9 Around 50% of reported cases of hypertension have a genetic component,10, 11, 12 while modifiable factors like lifestyle, diet, and physical activity (PA) contribute to the other half.13,14

The American Heart Association highlighted that the significance of HBP in children was previously underestimated. Recent studies show that many children and adolescents in the United States face hypertension risks. Data reveals that 5% of this demographic has HBP, while 18% exhibit elevated BP.15 Similarly, the Centers for Disease Control and Prevention reported that among youth aged 12–19, 1 in 25 has hypertension, and 1 in 10 experiences elevated BP.16 Considering these findings, both American Heart Association and Centers for Disease Control and Prevention emphasize the increasing incidence of HBP in young individuals, which could lead to health complications in adulthood. As a result, it’s imperative to implement preventive measures to counteract the rising trend of HBP in this age group. While medical research explores various approaches for monitoring and controlling genetically-based hypertension, non-medical approaches may be more feasible and effective in the interim.

Conclusion

Although medication-based treatments are essential for young individuals with hypertension, non-drug strategies have demonstrated effectiveness for lowering BP among healthy youth. Thus, integrating PA with other alterable factors early on can serve as a protective shield against future health issues. Notably, interventions that amalgamate PA, nutrition, and behavioral adjustments tend to be notably superior at decreasing both SBP and DBP compared to interventions focused solely on PA. Moreover, further investigation is required to classify PA modalities in terms of content, length, and intensity before concluding that PA-only intervention is the least effective approach for reducing BP.

Highlights

Abstract

Graphical abstract

Keywords

1. Introduction

2. Methods

3. Results

4. Discussion

5. Conclusion

Acknowledgments

Appendix. Supplementary materials

References

Abstract

Background
We compared body mass index (BMI), body fat, and skeletal muscle mass between (1) a mixed-sex nonathletic cohort of people with patellofemoral pain (PFP) and pain-free people, and (2) a nonathletic cohort of people with PFP and pain-free people subgrouped by sex (i.e., men and women with PFP vs. pain-free men and women).

Methods
This cross-sectional study included 114 people with PFP (71 women, 43 men) and 54 pain-free controls (32 women, 22 men). All participants attended a single testing session to assess body composition measures, which included BMI, percentage of body fat (%BFBioimpedance), and skeletal muscle mass (both assessed by bioelectrical impedance analysis), and percentage of body fat (%BFSkinfold) (assessed by skinfold caliper analysis). A one-way univariate analysis of covariance (age and physical activity levels as covariates) was used to compare body composition measures between groups (i.e., PFP vs. pain-free group; women with PFP vs. pain-free women; men with PFP vs. pain-free men).

Results
Women with PFP presented significantly higher BMI, %BFBioimpedance, and %BFSkinfold, and lower skeletal muscle mass compared to pain-free women (p ≤ 0.04; effect size = ‒0.47 to 0.85). Men with PFP and men and women combined had no differences in BMI, %BFBioimpedance, %BFSkinfold, and skeletal muscle mass compared to their respective pain-free groups (p > 0.05).

Conclusion
Our findings indicate that BMI and body composition measures should be considered as part of the evaluation and management of people with PFP, especially in women, who have demonstrated higher BMI and body fat and lower skeletal muscle mass compared to pain-free controls. Future studies should not assess body composition measures in a mixed-sex population without distinguishing men participants from women participants.

1. Introduction
The prevalence of overweight and obesity has been growing alarmingly across the world.1 In the past four decades, the number of adults with obesity worldwide has increased more than 6 times (100 million in 1975 to 671 million in 2016),1 whereas 1.3 billion adults (1 in 4) were considered overweight in 2016.1,2 Despite increasing the predisposition to multiple comorbidities,3,4 overweight and obesity are also detrimental to the musculoskeletal system,5, 6, 7 likely via both systemic and mechanical effects.8,9 Systemic effects include the production by adipose tissue of adipokines such as leptin10 and the amplification of the inflammation profile through an increase in the production of interleukin-611 and tumor necrosis factor-alpha.12 Both of these systemic changes are associated with deleterious effects to patellar cartilage (e.g., reduced patellar cartilage volume) and pain.13,14 Mechanically, the one joint most affected by overweight and obesity is the patellofemoral joint, which is subjected to loads 2 to 11 times bodyweight during stair ascent, squatting, and running activities.15, 16, 17

Highlights

Abstract

Keywords

1. Introduction

2. Methods

3. Results

4. Discussion

5. Conclusion

Ethical Approval

Consent

Funding

Author contribution

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgements

Appendix A. Supplementary data

References

Abstract

Aim
The aim of this study was to evaluate parental attitudes to the use and effects of technology on physical activity levels of children aged 7 to 11.

Methods
A web-based questionnaire was completed by parents of 7–11 year-old children who had access to technological devices. Pearson’s chi-square test was used to determine if there were differences based on child’s gender or parental occupation. Themes were identified and evaluated using content analysis.

Results
There were 197 respondents providing information on 231 children. Children commonly had access to at least 3 devices at home. 53.3% of respondents did not feel that technology use had an impact on the physical activity of their children compared to 46.8% who thought it had a negative effect. There were no difference based on child’s gender or parent occupation.

Conclusions
Most parents do not believe that technology use negatively impacts upon their child’s physical activity and suggest that enjoyment of physical activity and setting access rules account for this. However, a substantial number believe it has a negative impact and suggest less access to technology would result in an increase to activity levels. Technological interventions that include restrictive mediation approaches and strategies to enhance physical literacy may be beneficial.

1. Introduction

The department of Health and Social Care (Department of Health and Social Care, 2019) define physical activity as bodily movement produced by skeletal muscles that requires energy expenditure. It can take many forms, occurs in many, and has many purposes including daily activity, recreation and sport. Current guidelines recommended that children and young people participate in at least 60 minutes of physical activity a day (Department of Health and Social CareHealth Do, 2019). However Only 48.7% of children in England (Sport England, 2019a), 38% in Scotland (Bardsley et al., 2018), 51% in wales (The National Assembly for Wales, 2019) and 11.9% in Northern Ireland (Northern Ireland Statistics and Research Agency, 2018) met these recommendations. This problem is not restricted to the UK, as low levels of physical activity has been shown to be a global crisis which will likely continue to worsen (Guthold et al., 2018), driven by widening income inequality (Tomkinson et al., 2019). As a result, it is possible that the current generation of children may have a higher risk of developing non-communicable diseases that significantly impact on quality of life and risks premature death (Nechuta et al., 2015).

Currently, there is no consensus on the most effective way to increase childhood physical activity, despite a significant amount of published research. Research has shown that technology can reduce the impact of some key barriers to accessing healthcare (Jansen-Kosterink et al., 2016). A review of the use of technological interventions to improve physical activity suggested they offer 12–25% greater improvement in physical activity levels compared to non-technology interventions in adults; there were no difference between interactive, non-interactive or self-monitoring technologies (Hakala et al., 2016). This may provide an opportunity to draw on technological solutions in future behaviour change interventions to improve childhood physical activity, however, this has not yet been widely studied.