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  1. Shahrizaila N, Sobue G, Kuwabara S, Kim SH, Birks C, Fan DS, et al.
    J Neurol Neurosurg Psychiatry, 2016 08;87(8):821-30.
    PMID: 27093948 DOI: 10.1136/jnnp-2015-312751
    While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.
    Matched MeSH terms: Amyotrophic Lateral Sclerosis/complications*
  2. Rahman NA, Fauzi AA, Chung TY, Latif LA, Chan SC
    Aust J Gen Pract, 2020 2 3;49(1-2):48-53.
    PMID: 32008261 DOI: 10.31128/AJGP-07-19-4991
    BACKGROUND AND OBJECTIVES: Diabetic Charcot foot (DCF) can cause gross structural deformities of the foot and ankle. The main objective of this study was to identify complications of DCF and its associated factors.

    METHOD: This is a retrospective cohort study. Data on medical background, previous DCF treatment and complications were obtained. Multiple logistic regression analysis was performed to measure factors related to various complications of DCF.

    RESULTS: Ninety-eight patient records were retrieved. Of the 83 patients who were still alive, 75.9% (n = 63) had recurrent ulcers, 53.0% (n = 44) had undergone foot surgery and 45.8% (n = 38) had undergone amputation. Patients with a history of recurrent ulcers have the highest predilection to amputation (odds ratio: 8.5; 95% confidence interval: 1.8, 39.1).

    DISCUSSION: In terms of DCF complications, foot ulcers are an independent predictor of recurrent foot ulcers, foot surgery and amputation. Regular foot assessment of patients with DCF to prevent ulcers is strongly recommended.

    Matched MeSH terms: Amyotrophic Lateral Sclerosis/complications
  3. Abdul Wahid SF, Law ZK, Ismail NA, Lai NM
    Cochrane Database Syst Rev, 2019 Dec 19;12(12):CD011742.
    PMID: 31853962 DOI: 10.1002/14651858.CD011742.pub3
    BACKGROUND: Amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND), is a fatal disease associated with rapidly progressive disability, for which no definitive treatment exists. Current treatment approaches largely focus on relieving symptoms to improve the quality of life of those affected. The therapeutic potential of cell-based therapies in ALS/MND has not been fully evaluated, given the paucity of high-quality clinical trials. Based on data from preclinical studies, cell-based therapy is a promising treatment for ALS/MND. This review was first published in 2015 when the first clinical trials of cell-based therapies were still in progress. We undertook this update to incorporate evidence now available from randomised controlled trials (RCTs).

    OBJECTIVES: To assess the effects of cell-based therapy for people with ALS/MND, compared with placebo or no treatment.

    SEARCH METHODS: On 31 July 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched two clinical trials registries for ongoing or unpublished studies.

    SELECTION CRITERIA: We included RCTs that assigned people with ALS/MND to receive cell-based therapy versus a placebo or no additional treatment. Co-interventions were allowed, provided that they were given to each group equally.

    DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology.

    MAIN RESULTS: Two RCTs involving 112 participants were eligible for inclusion in this review. One study compared autologous bone marrow-mesenchymal stem cells (BM-MSC) plus riluzole versus control (riluzole only), while the other study compared combined intramuscular and intrathecal administration of autologous mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) to placebo. The latter study was reported as an abstract and provided no numerical data. Both studies were funded by biotechnology companies. The only study that contributed to the outcome data in the review involved 64 participants, comparing BM-MSC plus riluzole versus control (riluzole only). It reported outcomes after four to six months. It had a low risk of selection bias, detection bias and reporting bias, but a high risk of performance bias and attrition bias. The certainty of evidence was low for all major efficacy outcomes, with imprecision as the main downgrading factor, because the range of plausible estimates, as shown by the 95% confidence intervals (CIs), encompassed a range that would likely result in different clinical decisions. Functional impairment, expressed as the mean change in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score from baseline to six months after cell injection was slightly reduced (better) in the BM-MSC group compared to the control group (mean difference (MD) 3.38, 95% CI 1.22 to 5.54; 1 RCT, 56 participants; low-certainty evidence). ALSFRS-R has a range from 48 (normal) to 0 (maximally impaired); a change of 4 or more points is considered clinically important. The trial did not report outcomes at 12 months. There was no clear difference between the BM-MSC and the no treatment group in change in respiratory function (per cent predicted forced vital capacity; FVC%; MD -0.53, 95% CI -5.37 to 4.31; 1 RCT, 56 participants; low-certainty evidence); overall survival at six months (risk ratio (RR) 1.07, 95% CI 0.94 to 1.22; 1 RCT, 64 participants; low-certainty evidence); risk of total adverse events (RR 0.86, 95% CI 0.62 to 1.19; 1 RCT, 64 participants; low-certainty evidence) or serious adverse events (RR 0.47, 95% CI 0.13 to 1.72; 1 RCT, 64 participants; low-certainty evidence). The study did not measure muscle strength.

    AUTHORS' CONCLUSIONS: Currently, there is a lack of high-certainty evidence to guide practice on the use of cell-based therapy to treat ALS/MND. Uncertainties remain as to whether this mode of therapy is capable of restoring muscle function, slowing disease progression, and improving survival in people with ALS/MND. Although one RCT provided low-certainty evidence that BM-MSC may slightly reduce functional impairment measured on the ALSFRS-R after four to six months, this was a small phase II trial that cannot be used to establish efficacy. We need large, prospective RCTs with long-term follow-up to establish the efficacy and safety of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research are to determine the appropriate cell source, phenotype, dose and method of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.

    Matched MeSH terms: Amyotrophic Lateral Sclerosis/complications
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