Relative efficacy of different types of exercises in the treatment of knee and hip osteoarthritis: A network meta-analysis of randomised controlled trials

Background: The need for exercise in osteoarthritis (OA) has been long-recognised, leading international guidelines and experts to universally endorse exercise as a core treatment for OA. However, currently there is no consensus on which type of exercise is most beneficial, and there is clear differentiation of exercise effects across different OA outcomes. Objective: The primary objective was to estimate the relative efficacy of different exercises for pain, function, physical performance and quality of life (QoL) outcomes in people with knee and hip OA. This research aim was also accompanied by an update of the evidence in overall exercise versus usual care in conservatively managed OA and in those who had undergone joint replacement surgery. The primary time point was at, or nearest to, eight weeks. However, for analysis of post-joint replacements, the primary time point was three months. Method: A literature search was performed in nine electronic databases and hand searches without limitation in publication date or language. Exercises were classified into aerobic, strengthening, flexibility/skills (flex/skills), mind-body and mixed. Inclusion criteria to be fulfilled were: i) randomised controlled trials (RCTs) of knee OA or hip OA or mixed knee and hip OA, including postoperative participants; ii) RCTs comparing one type of exercise with another type, or other non-exercise interventions; and iii) provision of outcomes for pain, function, performance or QoL. The first search was performed in December 2015 and a final update was conducted in December 2017. Upon completion of screening, the most widely used non-exercise control group was identified to perform NMA. Effect size (ES) of exercise benefits was measured as standardised mean difference between groups and was reported along with 95% confidence intervals (CIs) for conventional meta-analysis (performed using frequentist approach), and with 95% credible interval (CrI) for network meta-analysis (performed using Bayesian approach). Results: In the first search, 13672 citations were identified from electronic databases and hand searches. After removal of duplicates and full texts screening, 199 citations (185 trials) met the inclusion criteria. After the update in December 2017 40 more eligible citations (32 trials) were added, giving a total of 239 citations (217 trials). However, only 106 trials were deemed eligible for analysis in this thesis because the focus was on the single most common non-exercise comparator used – usual care. In the conventional meta-analysis which was performed to examine the overall effect of exercise versus usual care, 77 trials (n=6472) contributed to the analysis. In the network meta-analysis that was performed to compare the relative efficacy of different exercises, 103 trials (n=9134) were included. Finally, in the meta-analysis of exercise versus usual care on postoperative outcomes, only nine trials (n=467) were eligible. Compared to usual care, exercise conferred higher ES for pain (ES 0.56; 95%CI 0.44, 0.68), function (ES 0.51; 95%CI 0.38-0.63) and performance (ES 0.46; 95%CI 0.35, 0.57) compared to QoL (ES 0.21; 95%CI 0.11, 0.31) at eight weeks. Single component exercise, particularly aerobic exercise, was most likely to be the most effective for improving OA outcomes. For many outcomes, the differences between different exercises were not statistically significant, except for pain where aerobic or mind–body exercise were significantly better than mixed exercise. These results were generally driven by studies on knee OA, and by strengthening and mixed exercises. Overall evidence indicates that exercise therapy had better benefits in people with knee OA, in people not on the waiting-list for surgery, and in trials with younger participants (mean age <60-years old). Peak benefits were demonstrated at 2-3 months after commencement of exercise and were likely to remain significantly better than usual care beyond this point for another three months. There were insufficient trials on subsets of hip OA and mixed OA, and OA awaiting surgery (mainly total joint replacement) to permit extensive analyses. The number of trials investigating postoperative outcomes was also small but were sufficient to be pooled for exploratory analysis. The results at three months after surgery suggest that there were no differences between groups given pre-operative exercise and groups given usual care. Although differences between groups were in favour of exercise for pain (ES 0.13), function (ES 0.25) and performance (ES 0.03), none were statistically significant. Conclusion: Exercise significantly improves pain, function and performance for knee and hip OA, with single component exercises (particularly aerobic exercise) being consistently better than mixed exercise. However, due to the small number of studies, the results for particular OA subsets (i.e. hip and mixed OA, OA awaiting total joint replacement and postoperative OA) were uncertain. This indirectly reflects the gap in the evidence and the need for future confirmatory studies

Microalgae as potential anti-inflammatory natural products against human inflammatory skin diseases

The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challenges with inefficient and inappropriate treatment in managing skin diseases. Overproduction of ROS in the body will result in oxidative stress which will lead to various cellular damage and alter normal cell function. Multiple signaling pathways are seen to have significant effects during ROS-mediated oxidative stress. In this review, microalgae have been selected as a source of natural-derived antioxidant to combat inflammatory skin diseases that are prominent in today's society. Several studies have demonstrated that bioactive compounds isolated from microalgae have anti-inflammation and anti-oxidative properties that can help remedy various skin diseases. These compounds are able to inhibit production of pro-inflammatory cytokines and reduce the expression of inflammatory genes. Bioactive compounds from microalgae work in action by altering enzyme activities, regulating cellular activities, targeting major signaling pathways related to inflammation

Transfer learning-assisted 3D deep learning models for knee osteoarthritis detection: Data from the osteoarthritis initiative

Knee osteoarthritis is one of the most common musculoskeletal diseases and is usually diagnosed with medical imaging techniques. Conventionally, case identification using plain radiography is practiced. However, we acknowledge that knee osteoarthritis is a 3D complexity; hence, magnetic resonance imaging will be the ideal modality to reveal the hidden osteoarthritis features from a three-dimensional view. In this work, the feasibility of well-known convolutional neural network (CNN) structures (ResNet, DenseNet, VGG, and AlexNet) to distinguish knees with and without osteoarthritis (OA) is investigated. Using 3D convolutional layers, we demonstrated the potential of 3D convolutional neural networks of 13 different architectures in knee osteoarthritis diagnosis. We used transfer learning by transforming 2D pre-trained weights into 3D as initial weights for the training of the 3D models. The performance of the models was compared and evaluated based on the performance metrics [balanced accuracy, precision, F1 score, and area under receiver operating characteristic (AUC) curve]. This study suggested that transfer learning indeed enhanced the performance of the models, especially for ResNet and DenseNet models. Transfer learning-based models presented promising results, with ResNet34 achieving the best overall accuracy of 0.875 and an F1 score of 0.871. The results also showed that shallow networks yielded better performance than deeper neural networks, demonstrated by ResNet18, DenseNet121, and VGG11 with AUC values of 0.945, 0.914, and 0.928, respectively. This encourages the application of clinical diagnostic aid for knee osteoarthritis using 3DCNN even in limited hardware conditions

Perceptions of Stigma Associated with Chronic Knee Pain: Voices of Selected Women in Thailand and Malaysia

Introduction A higher prevalence of knee pain in Southeast Asian countries, compared with non-Asian countries, is an established fact. This article hypothesizes that this fact, combined with personal, cultural, and environmental factors, may influence attitudes towards illness and treatment-seeking behaviour and adherence. Objective This study aimed to determine current attitudes, stigma, and barriers of women to the management of chronic knee pain and treatment in two Southeast Asian countries. Methods Fourteen semi-structured interviews explored female lived perceptions of chronic knee pain in Southeast Asia. Using a phenomenological reduction process, open-ended questions allowed participants to voice their perceptions of their experience of this knee condition. Particular foci were potential stigma associated with the perceptions of others, health-seeking attitudes, and attitudes towards exercise. Results The shared experiences of managing chronic knee pain revealed the impact of their condition on participants' normality of life and their struggles with pain, limitations, and fear for the future. Key individual, interpersonal, organisational and community barriers and facilitators impacted the health seeking attitudes and engagement with conservative rehabilitation programmes. Conclusion Improved socio-cultural competency and consideration for an individuals’ intersectional identity and interpersonal relationships are key to designing rehabilitation and conservative management solutions. Co-creating alternative pathways for rehabilitation for individuals that are more distant from health facilities may help reduce socio-cultural barriers at a community level

Efficacy and potential determinants of exercise therapy in knee and hip osteoarthritis: a systematic review and meta-analysis

Background. Exercise is an effective treatment for osteoarthritis. However, the effect may vary from one patient (or study) to another.Objective. To evaluate the efficacy of exercise and its potential determinants for pain, function, performance, and quality of life (QoL) in knee and hip osteoarthritis (OA).Methods. We searched 9 electronic databases (AMED, CENTRAL, CINAHL, EMBASE, MEDLINE Ovid, PEDro, PubMed, SPORTDiscus and Google Scholar) for reports of randomised controlled trials (RCTs) comparing exercise-only interventions with usual care. The search was performed from inception up to December 2017 with no language restriction. The effect size (ES), with its 95% confidence interval (CI), was calculated on the basis of between-group standardised mean differences. The primary endpoint was at or nearest to 8 weeks. Other outcome time points were grouped into intervals, from less than 1 month to ≥18 months, for time-dependent effects analysis. Potential determinants were explored by subgroup analyses. Level of significance was set at p≤0.10.Results. Data from 77 RCTs (6472 participants) confirmed statistically significant exercise benefits for pain (ES 0.56, 95% CI 0.44–0.68), function (0.50, 0.38–0.63), performance (0.46, 0.35–0.57), and QoL (0.21, 0.11–0.31) at or nearest to 8 weeks. Across all outcomes, the effects appeared to peak around 2 months and then gradually decreased and became no better than usual care after 9 months. Better pain relief was reported by trials investigating participants who were younger (mean age less than 60 years), had knee OA, and were not awaiting joint replacement surgery.Conclusions. Exercise significantly reduces pain and improves function, performance and QoL in people with knee and hip OA as compared with usual care at 8 weeks. The effects are maximal around 2 months and thereafter slowly diminish, being no better than usual care at 9 to 18 months. Participants with younger age, knee OA and not awaiting joint replacement may benefit more from exercise therapy. These potential determinants, identified by study-level analyses, may have implied ecological bias and need to be confirmed with individual patient data

Influence and implications of the renin–angiotensin–aldosterone system in obstructive sleep apnea : An updated systematic review and meta-analysis

Obstructive sleep apnea is a chronic, sleep-related breathing disorder, which is an independent risk factor for cardiovascular disease. The renin–angiotensin–aldosterone system regulates salt and water homeostasis, blood pressure, and cardiovascular remodelling. Elevated aldosterone levels are associated with excess morbidity and mortality. We aimed to analyse the influence and implications of renin–angiotensin–aldosterone system derangement in individuals with and without obstructive sleep apnea. We pooled data from 20 relevant studies involving 2828 participants (1554 with obstructive sleep apnea, 1274 without obstructive sleep apnea). The study outcomes were the levels of renin–angiotensin–aldosterone system hormones, blood pressure and heart rate. Patients with obstructive sleep apnea had higher levels of plasma renin activity (pooled wmd+ 0.25 [95% confidence interval 0.04–0.46], p = 0.0219), plasma aldosterone (pooled wmd+ 30.79 [95% confidence interval 1.05–60.53], p = 0.0424), angiotensin II (pooled wmd+ 5.19 [95% confidence interval 3.11–7.27], p < 0.001), systolic (pooled wmd+ 5.87 [95% confidence interval 1.42–10.32], p = 0.0098) and diastolic (pooled wmd+ 3.40 [95% confidence interval 0.86–5.94], p = 0.0086) blood pressure, and heart rate (pooled wmd+ 3.83 [95% confidence interval 1.57–6.01], p = 0.0009) compared with those without obstructive sleep apnea. The elevation remained significant (except for renin levels) when studies involving patients with resistant hypertension were removed. Sub-group analysis demonstrated that levels of angiotensin II were significantly higher only among the Asian population with obstructive sleep apnea compared with those without obstructive sleep apnea. Body mass index accounted for less than 10% of the between-study variance in elevation of the renin–angiotensin–aldosterone system parameters. Patients with obstructive sleep apnea have higher levels of renin–angiotensin–aldosterone system hormones, blood pressure and heart rate compared with those without obstructive sleep apnea, which remains significant even among patients without resistant hypertension

Relative efficacy of different exercises for pain, function, performance and quality of life in knee and hip osteoarthritis: systematic review and network meta-analysis

Background: Guidelines recommend exercise as a core treatment for osteoarthritis (OA). However, it is unclear which type of exercise is most effective, leading to inconsistency between different recommendations. Objectives: To investigate the relative efficacy of different exercises (aerobic, mind-body, strengthening, flexibility/skill, or mixed) for improving pain, function, performance and quality of life (Qol) for knee and hip OA at, or nearest to, 8 weeks. Methods: We searched nine electronic databases up until December 2017 for randomised controlled trials that compared exercise with usual care or with another exercise type. Bayesian network meta–analysis was used to estimate the relative effect size (ES) and corresponding 95% credibility interval (CrI) (PROSPERO registration: CRD42016033865) Findings: We identified and analysed 103 trials (9,134 participants). Aerobic exercise was most beneficial for pain (ES 1.11; 95%CrI 0.69, 1.54) and performance (1.05; 0.63, 1.48). Mind–body exercise, which had pain benefit equivalent to that of aerobic exercise (1.11; 0.63, 1.59), was the best for function (0.81; 0.27, 1.36). Strengthening and flexibility/skill exercises improved multiple outcomes at a moderate level. Mixed exercise was the least effective for all outcomes and had significantly less pain relief than aerobic and mind–body exercises. Trend for exercise hierarchy was significant for pain (p=0.01), but not for function (p=0.07), performance (p=0.06) or QoL (p=0.65) Conclusion:The effect of exercise varies according to the type of exercise and target outcome. Aerobic or mind–body exercise may be the best for pain and function improvements

Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials

Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown. Network meta-analysis. PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022. Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA. A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs). Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol. CRD42019135166

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions.

Summary Background Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01)

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions

Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation:This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor