Risk factors and laboratory test results associated with severe illness and mortality in COVID-19 patients: A systematic review.

BackgroundWe aimed to systematically review all relevant studies related to the risk factors and laboratory test results associated with severe illness and mortality in COVID-19 patients.MethodsWe utilised PubMed, Scopus, ProQuest, Wiley Online Library, ScienceDirect and MedRxiv to search for studies, with additional hand-searched journals. We included systematic reviews/meta-analyses, cohort and case control studies of suspected and/or confirmed COVID-19 cases with severe illness and/or mortality as outcomes. We included laboratory test results and risk factors. We assessed risk of bias using ROBIS-I and Newcastle-Ottawa Scale assessment tool. Type of study, risk of bias, and precision of results determined evidence sufficiency.ResultsOf 26 records included, sufficient evidence suggested the association between age >60 years, hypertension, coronary heart disease, DM, serum LDH 250-500 U/L, LDH >500 U/L, and lymphopenia (lymphocyte count ≤1.0 x 109 /L) and severe illness of COVID-19. CD3+CD8+ cell count ≤ 75 cell/µl, D-dimer > 1 mg/L, AKI stage 2 and 3, proteinuria ≥1+, hematuria ≥1+, and peak serum creatinine > 13.26 µmol/L are associated with mortality.ConclusionAge >60 years, hypertension, DM, and coronary heart disease are the risk factors for severe illness of COVID-19. Laboratory test results associated with severe illness are serum LDH 250-500 U/L, LDH >500 U/L, and lymphopenia, whereas test results associated with mortality are CD3+CD8+ cell count ≤ 75 cell/µl, AKI stage 2 and 3, proteinuria ≥1+, hematuria ≥1+, D-dimer > 1 mg/L, peak serum creatinine > 13.26 µmol/L.

Oral prednisolone for acute otitis media in children: a pilot, pragmatic, randomised, open-label, controlled study (OPAL study).

BACKGROUND: Acute otitis media (AOM) is associated with high antibiotic prescribing rates. Antibiotics are somewhat effective in improving pain and middle ear effusion (MEE); however, they have unfavourable effects. Alternative treatments, such as corticosteroids as anti-inflammatory agents, are needed. Evidence for the efficacy of these remains inconclusive. We conducted a pilot study to test feasibility of a proposed large-scale randomised controlled trial (RCT) to assess the efficacy of corticosteroids for AOM. METHODS: We conducted a pilot, pragmatic, parallel, open-label RCT of oral corticosteroids for paediatric AOM in primary and secondary/tertiary care centres in Indonesia. Children aged 6 months-12 years with AOM were randomised to either prednisolone or control (1:1). Physicians were blinded to allocation. Our objectives were to test the feasibility of our full RCT procedures and design, and assess the mechanistic effect of corticosteroids, using tympanometry, in suppressing middle ear inflammation by reducing MEE. RESULTS: We screened 512 children; 62 (38%) of 161 eligible children were randomised and 60 were analysed for the primary clinical outcome. All study procedures were completed successfully by healthcare personnel and parents/caregivers, despite time constraints and high workload. All eligible, consenting children were appropriately randomised. One child did not take the medication and four received additional oral corticosteroids. Our revised sample size calculation verified 444 children are needed for the full RCT. Oral corticosteroids did not have any discernible effects on MEE resolution and duration. There was no correlation between pain or other symptoms and MEE change. However, prednisolone may reduce pain intensity at day 3 (Visual Analogue Scale mean difference - 7.4 mm, 95% confidence interval (CI) - 13.4 to - 1.3, p = 0.018), but cause drowsiness (relative risk (RR) 1.8, 95% CI 1.1 to 2.8, p = 0.016). Tympanometry curves at day 7 may be improved (RR 1.8, 95% CI 1.0 to 2.9). We cannot yet confirm these as effects of corticosteroids due to insufficient sample size in this pilot study. CONCLUSIONS: It is feasible to conduct a large, pragmatic RCT of corticosteroids for paediatric AOM in Indonesia. Although oral corticosteroids may reduce pain and improve tympanometry curves, it requires an adequately powered clinical trial to confirm this. TRIAL REGISTRATION: Study registry number: ACTRN12618000049279. Name of registry: the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration: 16 January 2018.

Oral prednisolone for acute otitis media in children: protocol of a pilot randomised, open-label, controlled study (OPAL study).

BACKGROUND: Acute otitis media (AOM) is an acute inflammation of the middle ear commonly found in children, for which antibiotics are frequently prescribed. However, antibiotics are beneficial for only one third of AOM cases, and then, with only modest benefit. Since antibiotic use leads to risk of side effects and resistance, effective alternative treatments are required. Corticosteroids are a candidate because of their anti-inflammatory effects, although evidence of their efficacy and harms is insufficient. Accordingly, we plan a large, rigorous clinical trial to test this. Initially, we will test pre-specified methods and procedures (including the overall process, resources, management, and scientific components) in a pilot study of corticosteroids for AOM, which will inform a future, definitive trial. METHODS: This is a pilot pragmatic, randomised, open-label, single-blind, controlled study of corticosteroids as either monotherapy or an addition to antibiotics in 60 children aged 6 months to 12 years with AOM in two cities (Jakarta and Bekasi) in Indonesia. We will randomise eligible children to prednisolone or control. We will also stratify by disease severity and randomise those with mild AOM to expectant observation plus prednisolone or observation alone and those with severe AOM to prednisolone plus antibiotic or antibiotic alone. Our outcomes are to determine (1) recruitment rates, (2) the success of the study procedures, (3) the ability to measure planned outcomes of the proposed main study, (4) the compliance to study visits and study medication, and (5) verification of the sample size calculation for the main study. We will also assess middle ear effusion using tympanometry as part of a mechanistic sub-study. DISCUSSION: This study will test all procedures in preparation for the main study, including several potential obstacles and challenges from the perspective of participating physicians, nurses, pharmacists, and the parents of eligible children. This information will be useful for developing strategies to overcome practical and procedural issues. This study may also provide information about the effects of corticosteroids on middle ear effusion in AOM. TRIAL REGISTRATION: Study registry number: ACTRN12618000049279. Name of registry: the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration: 16 January 2018.

Systemic corticosteroids for acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti-inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics. OBJECTIVES: To assess the effects of systemic corticosteroids (oral or parenteral), with or without antibiotics, for AOM in children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane ARI Group's Specialised Register, MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Thomson Reuters), and LILACS (BIREME) for published studies, and ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing studies, to 20 February 2018. We checked the reference lists of all primary studies and review articles for additional references and contacted experts in the field to identify additional unpublished materials. SELECTION CRITERIA: We included randomised controlled trials of children with AOM that compared any systemic corticosteroid (oral or parenteral) with placebo, either with antibiotics (corticosteroid plus antibiotic versus placebo plus antibiotic) or without antibiotics (corticosteroid versus placebo). DATA COLLECTION AND ANALYSIS: Three review authors (EDS, RR, YP) independently screened the titles and abstracts and retrieved the full texts of potentially relevant studies. We independently extracted study characteristics and outcome data from the included studies, and assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed study quality using the GRADE method. MAIN RESULTS: We included two studies involving 252 children with AOM aged from three months to six years receiving hospital ambulatory care who were treated with intramuscular ceftriaxone, and who were then randomised to the corticosteroid group (corticosteroid and corticosteroid plus antihistamine) or the placebo group (antihistamine and double placebo). In one study, children also had a needle aspiration of middle ear fluid. Both studies were at unclear risk of bias for allocation concealment, and unclear to high risk of bias for selective reporting.One study (N = 179) included pain as an outcome, but we were unable to derive the proportion of children with persistent pain at Day 5 and Day 14. Reduction of overall or specific symptoms was presented as improvement in clinical symptoms and resolution of inflamed tympanic membranes without the need for additional antibiotic treatment: at Day 5 (94% of children in the treatment group (N = 89) versus 89% in the placebo group (N = 90); risk ratio (RR) 1.06, 95% confidence interval (CI) 0.97 to 1.16) and Day 14 (91% versus 87%; RR 1.05, 95% CI 0.95 to 1.17). Low-quality evidence meant that we are uncertain of the effectiveness of corticosteroids for this outcome.The second study (N = 73) reported a reduction of overall or specific symptoms without additional antibiotic treatment during the first two weeks as a favourable outcome. Children in the treatment group had more favourable outcomes (adjusted odds ratio 65.9, 95% CI 1.28 to 1000; P = 0.037), although the numbers were small. We were unable to pool the results with the other study because it did not report the proportion of children with this outcome by treatment group. Only one study reported adverse effects of corticosteroids (e.g. drowsiness, nappy rash), but did not quantify incidence, so we were unable to draw conclusions about adverse effects. Neither study reported a reduction in overall or specific symptom duration. AUTHORS' CONCLUSIONS: The evidence for the effect of systemic corticosteroids on AOM is of low to very low quality, meaning the effect of systemic corticosteroids on important clinical outcomes in AOM remains uncertain. Large, high-quality studies are required to resolve the question.

Exercise Intervention for Chronic Pain Management, Muscle Strengthening, and Functional Score in Obese Patients with Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis.

BACKGROUND: obesity and osteoarthritis have strong inter-relationship with multi-factorial mechanism that caused pain and leads to decreased quality of life. Exercise has been identified as prevention and management against obesity and joint pain. This systematic review aims to assess the effect between exercises compared to diet group for chronic pain management, physical and mental function in obese patients with chronic musculoskeletal problem. METHODS: we performed a systematic search of Randomized Control Trial studies from Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EBSCO; SCIENCEDIRECT (Elsevier); SCOPUS, grey literature, trial registry, ongoing study for published studies, and from the ClinicalTrial.gov, thesis of rehabilitation medicine in RSCM, and proceeding books for unpublished studies that was last updated on November 2016. Risk of bias was assessed using Cochrane risk-of-bias tool and data were analyzed using Review Manager 2014. RESULTS: one study showed no difference in pain reduction (assessed using VAS) between two groups. Two studies showed improvement in physical function measured using 6MWT in exercise group at 6 and 18 months with mean difference 28.12 [11.20, 45.04] and 26.21 [9.01, 43.41]. There was no significant effects observed for Mental and Physical Function based on SF-36 after 6 months (1 study) and 18 months (2 studies) observation, with mean difference 1.10 [-0.79, 2.99] and 0.08 [-1.53, 1.70] respectively for Mental Function score and -0.30 [-2.54, 1.94]  and -0.36 [-2.30, 1.57] respectively for Physical Function score. CONCLUSION: exercise can improve physical function objectively, but could not reduce pain in obese patients with chronic musculoskeletal problem subjectively.