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  1. Monica S, Jojo PJ, Khandaker MU
    Int J Radiat Biol, 2020 08;96(8):1028-1037.
    PMID: 32394771 DOI: 10.1080/09553002.2020.1767816
    Purpose: Ayurveda is one of the oldest systems of medicines in the world being practiced widely in the Indian subcontinent for more than 3000 years, and still remains as one of the important traditional health care systems. The Ayurvedic drugs are derived primarily from various parts of the plants, like root, leaf, flower, fruit or plant as a whole. Plants uptake minerals and other nutrients from the soil through their root system. Along with other minerals radionuclides present in the growing media also reach to the plant parts following the same pathway. Realizing the probable health hazards via the intake of Ayurvedic drugs, it is important to assess the concentration of natural radionuclides in commonly used medicinal plants.Materials and methods: NaI(Tl) scintillator-based gamma-ray spectrometry has been used to determine the activity concentrations of primordial radionuclides (226Ra, 232Th and 40K) in the most commonly used medicinal plant parts as ingredients of Ayurvedic medicines in India.Results and discussion: The average specific activity (Bqkg-1) of 226Ra, 232Th and 40K was found to be 43 ± 18, 36 ± 15[Formula: see text] and 230 ± 46, respectively. The estimated annual committed effective doses due to the intake of common Ayurvedic medicines at prescribed dosage was found to be 39 ± 16 µSv y-1,[Formula: see text] which is quite low as compared with the radiation dose limit of 1 mSvy-1 from all natural sources, reported by the International Commission on Radiological Protection (ICRP-60).Conclusions: It is found categorically that intake of Ayurvedic medicines at normal dosage poses no radiological hazard to the individual. Present results are significant in the wake of myths that many hazardous materials including radioisotopes are present at higher levels. Obtained results also serve as a reference information for the distribution of radionuclides in medicinal plant species.
  2. Goh SL, Persson MSM, Stocks J, Hou Y, Lin J, Hall MC, et al.
    Ann Phys Rehabil Med, 2019 Sep;62(5):356-365.
    PMID: 31121333 DOI: 10.1016/j.rehab.2019.04.006
    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<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<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.

  3. Goh SL, Persson MS, Bhattacharya A, Hall M, Doherty M, Zhang W
    Syst Rev, 2016 09 02;5(1):147.
    PMID: 27590834 DOI: 10.1186/s13643-016-0321-6
    BACKGROUND: 'Exercise' is universally recommended as a core treatment for knee and hip osteoarthritis (OA). However, there are very few head-to-head comparative trials to determine the relative efficacy between different types of exercise. The aim of this study is to benchmark different types of exercises against each other through the use of a common comparator in a network meta-analysis of randomised controlled trials (RCTs).

    METHODS: This study will include only RCTs published in peer-reviewed journals. A systematic search will be conducted in several electronic databases and other relevant online resources. No limitations are imposed on language or publication date. Participants must be explicitly identified by authors as having OA. Interventions that involved exercise or comparators in any form will be included. Pain is the primary outcome of interest; secondary outcomes will include function and quality of life measures. Quality assessment of studies will be based on the modified Cochrane's risk of bias assessment tool. At least two investigators will be involved throughout all stages of screening and data acquisition. Conflicts will be resolved through discussion. Conventional meta-analysis will be performed based on random effects model and network meta-analysis on a Bayesian model. Subgroup analysis will also be conducted based on study, patient and disease characteristics.

    DISCUSSION: This study will provide for the first time comprehensive research evidence for the relative efficacy of different exercise regimens for treatment of OA. We will use network meta-analysis of existing RCT data to answer this question.

    SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033865.

  4. Persson MS, Fu Y, Bhattacharya A, Goh SL, van Middelkoop M, Bierma-Zeinstra SM, et al.
    Syst Rev, 2016 Sep 26;5(1):165.
    PMID: 27686859
    BACKGROUND: Pain is the most troubling issue to patients with osteoarthritis (OA), yet current pharmacological treatments offer only small-to-moderate pain reduction. Current guidelines therefore emphasise the need to identify predictors of treatment response. In line with these recommendations, an individual patient data (IPD) meta-analysis will be conducted. The study aims to investigate the relative treatment effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) and topical capsaicin in OA and to identify patient-level predictors of treatment response.
    METHODS: IPD will be collected from randomised controlled trials (RCTs) of topical NSAIDs and capsaicin in OA. Multilevel regression modelling will be conducted to determine predictors for the specific and the overall treatment effect.
    DISCUSSION: Through the identification of treatment responders, this IPD meta-analysis may improve the current understanding of the pain mechanisms in OA and guide clinical decision-making. Identifying and prescribing the treatment most likely to be beneficial for an individual with OA will improve the efficiency of patient management.
    SYSTEMATIC REVIEW REGISTRATION:
    CRD42016035254.
    KEYWORDS: Capsaicin; Individual patient data meta-analysis; NSAIDs; Osteoarthritis; Topical
  5. Goh SL, Persson MSM, Stocks J, Hou Y, Welton NJ, Lin J, et al.
    Sports Med, 2019 May;49(5):743-761.
    PMID: 30830561 DOI: 10.1007/s40279-019-01082-0
    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: The aim of this systematic review and network meta-analysis was 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 (9134 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. The trend 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. Strengthening and flexibility/skill exercises may be used for multiple outcomes. Mixed exercise is the least effective and the reason for this merits further investigation.

  6. Weng Q, Goh SL, Wu J, Persson MSM, Wei J, Sarmanova A, et al.
    Br J Sports Med, 2023 Aug;57(15):990-996.
    PMID: 36593092 DOI: 10.1136/bjsports-2022-105898
    OBJECTIVE: 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.

    DESIGN: Network meta-analysis.

    DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.

    ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.

    RESULTS: 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).

    CONCLUSIONS: 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.

  7. Fu Y, Persson MS, Bhattacharya A, Goh SL, Stocks J, van Middelkoop M, et al.
    Syst Rev, 2016 10 28;5(1):183.
    PMID: 27793184
    BACKGROUND: The management of osteoarthritis (OA) is unsatisfactory, as most treatments are not clinically effective over placebo and most drugs have considerable side effects. On average, 75 % of the analgesic effect from OA treatments in clinical trials can be attributed to a placebo response, and this response varies greatly from patient to patient. This individual patient data (IPD) meta-analysis aims to identify placebo responders and the potential determinants of the placebo response in OA.

    METHODS: This study is undertaken in conjunction with the OA Trial Bank, an ongoing international consortium aiming to collect IPD from randomised controlled trials (RCTs) for all treatments of OA. RCTs for each treatment of OA have been systematically searched for, and authors of the relevant trials have been contacted to request the IPD. We will use the IPD of placebo-controlled RCTs held by the OA Trial Bank for this project. The IPD in placebo groups will be used to investigate the placebo response according to the minimum clinically important difference (MCID) threshold (e.g. 20 % pain reduction). Responders to placebo will be compared with non-responders to identify predictors of response. The quality of the trials will be assessed and potential determinants will be examined using multilevel logistic regression analyses.

    DISCUSSION: This study explores the varying magnitude of the placebo response and the proportion of participants that experience a clinically important placebo effect in OA RCTs. Potential determinants of the placebo response will also be investigated. These determinants may be useful for future studies as it may allow participants to be stratified into groups based on their likely response to placebo. The results of this study may also be useful for pharmaceutical companies, who could improve the design of their studies in order to separate the specific treatment from the non-specific contextual (i.e. placebo) effects.

    SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033212.
  8. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al.
    Lancet, 2014 Sep 13;384(9947):980-1004.
    PMID: 24797575 DOI: 10.1016/S0140-6736(14)60696-6
    BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.

    METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.

    FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.

    INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

    FUNDING: Bill & Melinda Gates Foundation.

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