METHODOLOGY: Pubmed, Medline, SPORTDiscus and Google scholar were searched from inception to 4th January 2021 for randomised controlled trials (RCTs) involving injection therapies (e.g. blood derivatives, corticosteroid, hyaluronic acid, botulinum toxin) for CSTI. The primary and secondary outcomes were pain and function, respectively, at (or nearest to) 6 months. Effect size (ES) was presented as standardised mean difference with 95% confidence interval (CI). Frequentist random effect NMA was used to generate the overall estimates, subgroup estimates (by region and measurement time point) and sensitivity analyses.
RESULTS: A total of 91 articles (87 RCTs; 5859 participants) involving upper limb (74%), lower limb (23%) and truncal/hip (3%) injuries were included. At all time points, prolotherapy had no statistically significant pain benefits over other therapies. This observation remained unchanged when tested under various assumptions and with exclusion of studies with high risk of bias. Although prolotherapy did not offer statistically significant functional improvement compared to most therapies, its ES was consistently better than non-injections and corticosteroid injection for both outcomes. At selected time points and for selected injuries, prolotherapy demonstrated potentially better pain improvement over placebo (<4 months: shoulder [ES 0.65; 95% CI 0.00 to 1.30]; 4-8 months: elbow [ES 0.91; 95% CI 0.12 to 1.70]; >8 months: shoulder [ES 2.08; 95% CI 1.49, to 2.68]). Injections generally produced greater ES when combined with non-injection therapy.
CONCLUSION: While clinical outcomes were generally comparable across types of injection therapy, prolotherapy may be used preferentially for selected conditions at selected times.
METHODS: This is a retrospective observational study involving 58 pregnancies from 1st January 2013 to 31st December 2019. Inclusion criteria were previous mid-trimester miscarriage and/or preterm birth, previous cervical surgery or short cervical length on routine sonogram. The demographic data, characteristics of each pregnancy and details of outcomes and management were described.
RESULTS: The majority of women were Malay with mean age and body mass index of 32.9 ± 4.2 years and 27.1 ± 6.3 kg/m2 respectively. The most frequent indications for Arabin pessary insertion were previous mid-trimester miscarriage (46.4%) and early preterm birth (17.2%). A total of 73.4% of these women had the pessary inserted electively at a mean cervical length of 31.6 ± 9.1 mm at median gestation of 15.0 weeks. They were managed as outpatient (56.9%), inpatient (24.1%) or mixed (19.0%) with combination of progestogen (81.0%) and 53.4% received antenatal corticosteroids. Spontaneous preterm birth at or more than 34 weeks gestation occurred in 74.1% with birthweight at or more than 2000 g (82.4%). Despite cervical funneling in 12 women (20.7%), 66.7% delivered at or later than 34 weeks gestation and 2 (16.7%) resulted in miscarriage.
CONCLUSIONS: Insertion of the Arabin pessary is beneficial to prevent spontaneous preterm birth in pregnant women who are at high risk. In particular, early insertion and close monitoring allows the best possible outcomes.
TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov ( NCT04638023 ) on 20/11/2020.
METHODS: In this phase Ib, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1-letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).
RESULTS: The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4-point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (-36.3% versus -24.7%) and the SLEDAI score (-47.8% versus -10.7%) and in tender (-22.8% versus -13.5%) and swollen (-62.1% versus -7.8%) joint counts on day 169.
CONCLUSION: AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.
OBJECTIVES: To assess the effects of peri-operative tranexamic acid versus no therapy or placebo on operative parameters in patients with chronic rhinosinusitis (with or without nasal polyps) who are undergoing functional endoscopic sinus surgery (FESS).
SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 10 February 2022.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing intravenous, oral or topical tranexamic acid with no therapy or placebo in the treatment of patients (adults and children) with chronic rhinosinusitis, with or without nasal polyps, undergoing FESS.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Primary outcome measures were surgical field bleeding score (e.g. Wormald or Boezaart grading system), intraoperative blood loss and significant adverse effects (seizures or thromboembolism within 12 weeks of surgery). Secondary outcomes were duration of surgery, incomplete surgery, surgical complications and postoperative bleeding (placing of packing or revision surgery) in the first two weeks after surgery. We performed subgroup analyses for methods of administration, different dosages, different forms of anaesthesia, use of thromboembolic prophylaxis and children versus adults. We evaluated each included study for risk of bias and used GRADE to assess the certainty of the evidence.
MAIN RESULTS: We included 14 studies in the review, with a total of 942 participants. Sample sizes in the included studies ranged from 10 to 170. All but two studies included adult patients (≥ 18 years). Two studies included children. Most studies had more male patients (range 46.6% to 80%). All studies were placebo-controlled and four studies had three treatment arms. Three studies investigated topical tranexamic acid; the other studies reported the use of intravenous tranexamic acid. For our primary outcome, surgical field bleeding score measured with the Boezaart or Wormald grading score, we pooled data from 13 studies. The pooled result demonstrated that tranexamic acid probably reduces the surgical field bleeding score, with a standardised mean difference (SMD) of -0.87 (95% confidence interval (CI) -1.23 to -0.51; 13 studies, 772 participants; moderate-certainty evidence). A SMD below -0.70 represents a large effect (in either direction). Tranexamic acid may result in a slight reduction in blood loss during surgery compared to placebo with a mean difference (MD) of -70.32 mL (95% CI -92.28 to -48.35 mL; 12 studies, 802 participants; low-certainty evidence). Tranexamic acid probably has little to no effect on the development of significant adverse events (seizures or thromboembolism) within 24 hours of surgery, with no events in either group and a risk difference (RD) of 0.00 (95% CI -0.02 to 0.02; 8 studies, 664 participants; moderate-certainty evidence). However, there were no studies reporting significant adverse event data with a longer duration of follow-up. Tranexamic acid probably results in little difference in the duration of surgery with a MD of -13.04 minutes (95% CI -19.27 to -6.81; 10 studies, 666 participants; moderate-certainty evidence). Tranexamic acid probably results in little to no difference in the incidence of incomplete surgery, with no events in either group and a RD of 0.00 (95% CI -0.09 to 0.09; 2 studies, 58 participants; moderate-certainty evidence) and likely results in little to no difference in surgical complications, again with no events in either group and a RD of 0.00 (95% CI -0.09 to 0.09; 2 studies, 58 participants; moderate-certainty evidence), although these numbers are too small to draw robust conclusions. Tranexamic acid may result in little to no difference in the likelihood of postoperative bleeding (placement of packing or revision surgery within three days of surgery) (RD -0.01, 95% CI -0.04 to 0.02; 6 studies, 404 participants; low-certainty evidence). There were no studies with longer follow-up.
AUTHORS' CONCLUSIONS: There is moderate-certainty evidence to support the beneficial value of topical or intravenous tranexamic acid during endoscopic sinus surgery with respect to surgical field bleeding score. Low- to moderate-certainty evidence suggests a slight decrease in total blood loss during surgery and duration of surgery. Whilst there is moderate-certainty evidence that tranexamic acid does not lead to more immediate significant adverse events compared to placebo, there is no evidence regarding the risk of serious adverse events more than 24 hours after surgery. There is low-certainty evidence that tranexamic acid may not change postoperative bleeding. There is not enough evidence available to draw robust conclusions about incomplete surgery or surgical complications.
DESIGN: Systematic review and meta-analysis.
SETTING: Electronic search for randomized controlled trials and observational studies (MEDLINE, EMBASE, CENTRAL).
PARTICIPANTS: Hospitalized adults ≥ 18 years old who were SARS-CoV-2 PCR positive.
INTERVENTIONS: High-dose and low-dose corticosteroids.
MEASUREMENTS AND MAIN RESULTS: A total of twelve studies (n=2759 patients) were included in this review. The pooled analysis demonstrated no significant difference in mortality rate between the high-dose and low-dose corticosteroids groups (n=2632; OR: 1.07 [95%CI 0.67, 1.72], p=0.77, I2=76%, trial sequential analysis=inconclusive). No significant differences were observed in the incidence of intensive care unit (ICU) admission rate (n=1544; OR: 0.77[95%CI 0.43, 1.37], p=0.37, I2= 72%), duration of hospital stay (n=1615; MD: 0.53[95%CI -1.36, 2.41], p=0.58, I2=87%), respiratory support (n=1694; OR: 1.51[95%CI 0.77, 2.96], p=0.23, I2=84%), duration of mechanical ventilation (n=419; MD: -1.44[95%CI -4.27, 1.40], p=0.32, I2=93%), incidence of hyperglycemia (n=516, OR: 0.91[95%CI 0.58, 1.43], p=0.68, I2=0%) and infection rate (n=1485, OR: 0.86[95%CI 0.64, 1.16], p=0.33, I2=29%).
CONCLUSION: The meta-analysis demonstrated high-dose corticosteroids did not reduce mortality rate. However, high-dose corticosteroids did not pose higher risk of hyperglycemia and infection rate for COVID-19 patients. Due to the inconclusive trial sequential analysis, substantial heterogeneity and low level of evidence, future large-scale randomized clinical trials are warranted to improve the certainty of evidence for the use of high-dose compared to low-dose corticosteroids in COVID-19 patients.
METHODS: This was a planned sub-study of patients with an ED diagnosis of AECOPD identified in the Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study. The AANZDEM was a prospective, interrupted time series cohort study conducted in 46 ED in Australia, New Zealand, Singapore, Hong Kong and Malaysia over three 72-h periods in May, August and October 2014. Primary outcomes were patient epidemiology, clinical features, treatment and outcomes (hospital length of stay (LOS) and mortality).
RESULTS: Forty-six ED participated. There were 415 patients with an ED primary diagnosis of AECOPD (13.6% of the overall cohort; 95% CI: 12.5-14.9%). Median age was 73 years, 60% males and 65% arrived by ambulance. Ninety-one percent had an existing COPD diagnosis. Eighty percent of patients received inhaled bronchodilators, 66% received systemic corticosteroids and 57% of those with pH < 7.30 were treated with non-invasive ventilation (NIV). Seventy-eight percent of patients were admitted to hospital, 7% to an intensive care unit. In-hospital mortality was 4% and median LOS was 4 days (95% CI: 2-7).
CONCLUSION: Patients treated in ED for AECOPD commonly arrive by ambulance, have a high admission rate and significant in-hospital mortality. Compliance with evidence-based treatments in ED is suboptimal affording an opportunity to improve care and potentially outcomes.
MATERIALS AND METHODS: Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique.
RESULTS: Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA.
CONCLUSION: These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.