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  1. Morton SE, Chiew YS, Pretty C, Moltchanova E, Scarrott C, Redmond D, et al.
    Math Biosci, 2017 02;284:21-31.
    PMID: 27301378 DOI: 10.1016/j.mbs.2016.06.001
    Randomised control trials have sought to seek to improve mechanical ventilation treatment. However, few trials to date have shown clinical significance. It is hypothesised that aside from effective treatment, the outcome metrics and sample sizes of the trial also affect the significance, and thus impact trial design. In this study, a Monte-Carlo simulation method was developed and used to investigate several outcome metrics of ventilation treatment, including 1) length of mechanical ventilation (LoMV); 2) Ventilator Free Days (VFD); and 3) LoMV-28, a combination of the other metrics. As these metrics have highly skewed distributions, it also investigated the impact of imposing clinically relevant exclusion criteria on study power to enable better design for significance. Data from invasively ventilated patients from a single intensive care unit were used in this analysis to demonstrate the method. Use of LoMV as an outcome metric required 160 patients/arm to reach 80% power with a clinically expected intervention difference of 25% LoMV if clinically relevant exclusion criteria were applied to the cohort, but 400 patients/arm if they were not. However, only 130 patients/arm would be required for the same statistical significance at the same intervention difference if VFD was used. A Monte-Carlo simulation approach using local cohort data combined with objective patient selection criteria can yield better design of ventilation studies to desired power and significance, with fewer patients per arm than traditional trial design methods, which in turn reduces patient risk. Outcome metrics, such as VFD, should be used when a difference in mortality is also expected between the two cohorts. Finally, the non-parametric approach taken is readily generalisable to a range of trial types where outcome data is similarly skewed.
    Matched MeSH terms: Randomized Controlled Trials as Topic/statistics & numerical data*
  2. Lee YL, Lim YMF, Law KB, Sivasampu S
    Trials, 2020 Jun 16;21(1):530.
    PMID: 32546189 DOI: 10.1186/s13063-020-04349-4
    INTRODUCTION: There are few sources of published data on intra-cluster correlation coefficients (ICCs) amongst patients with type 2 diabetes (T2D) and/or hypertension in primary care, particularly in low- and middle-income countries. ICC values are necessary for determining the sample sizes of cluster randomized trials. Hence, we aim to report the ICC values for a range of measures from a cluster-based interventional study conducted in Malaysia.

    METHOD: Baseline data from a large study entitled Evaluation of Enhanced Primary Health Care interventions in public health clinics (EnPHC-EVA: Facility) were used in this analysis. Data from 40 public primary care clinics were collected through retrospective chart reviews and a patient exit survey. We calculated the ICCs for processes of care, clinical outcomes and patient experiences in patients with T2D and/or hypertension using the analysis of variance approach.

    RESULTS: Patient experience had the highest ICC values compared to processes of care and clinical outcomes. The ICC values ranged from 0.01 to 0.48 for processes of care. Generally, the ICC values for processes of care for patients with hypertension only are higher than those for T2D patients, with or without hypertension. However, both groups of patients have similar ICCs for antihypertensive medications use. In addition, similar ICC values were observed for clinical outcomes, ranging from 0.01 to 0.09. For patient experience, the ICCs were between 0.03 (proportion of patients who are willing to recommend the clinic to their friends and family) and 0.25 (for Patient Assessment of Chronic Illness Care item 9, Given a copy of my treatment plan).

    CONCLUSION: The reported ICCs and their respective 95% confidence intervals for T2D and hypertension will be useful for estimating sample sizes and improving efficiency of cluster trials conducted in the primary care setting, particularly for low- and middle-income countries.

    Matched MeSH terms: Randomized Controlled Trials as Topic/statistics & numerical data*
  3. Jadhav RA, Maiya GA, Hombali A, Umakanth S, Shivashankar KN
    Acta Diabetol, 2021 Apr;58(4):419-429.
    PMID: 33211181 DOI: 10.1007/s00592-020-01626-1
    AIMS: Inflammatory stage in prediabetes is associated with increase in level of adipokines and pro-inflammatory cytokines. Physical activity promotion considered as a first-line therapeutic strategy to treat prediabetes. We have conducted the systematic review and meta-analysis to strengthen the evidence on the impact of physical activity promotion on inflammatory markers in prediabetes.

    METHODS: Studies were identified using electronic search and manual search techniques by choosing keywords for prediabetes, physical activity and inflammatory marker. Randomized controlled trials on individuals diagnosed with prediabetes and provided intervention in the form of physical activity were included in this review. Adiponectin, leptin, C-reactive protein, interleukin-6 and tumour necrosis factor-α were the considered outcome measures.

    RESULTS: Our search retrieved 1,688 citations, 31 full-text articles assessed for eligibility of inclusion. Nine studies satisfied the pre-specified criteria for inclusion. Meta-analysis found that physical activity with or without dietary or lifestyle modification reduces level of leptin (MD-2.11 ng/mL, 95% CI -3.81 - -0.42) and interleukin-6 (MD -0.15 pg/mL, 95% CI -0.25--0.04). It has no effect on level of adiponectin (MD 0.26 µg/mL, 95% CI -0.42- 0.93), C-reactive protein (MD -0.05 mg/L, 95% CI -0.33-0.23) and tumour necrosis factor-α (MD 0.67 pg/mL, 95% CI -2.56-3.89).

    CONCLUSIONS: This review suggests that physical activity promotion with dietary and lifestyle modification may reduce the level of leptin and interleukin-6 but are uncertain if there is any effect on levels of adiponectin, C-reactive protein and tumour necrosis factor-α in the individuals with prediabetes.

    Matched MeSH terms: Randomized Controlled Trials as Topic/statistics & numerical data
  4. Kumbargere Nagraj S, Eachempati P, Paisi M, Nasser M, Sivaramakrishnan G, Verbeek JH
    Cochrane Database Syst Rev, 2020 Oct 12;10(10):CD013686.
    PMID: 33047816 DOI: 10.1002/14651858.CD013686.pub2
    BACKGROUND: Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk.

    OBJECTIVES: To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication.

    SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility.

    DATA COLLECTION AND ANALYSIS: Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity.

    MAIN RESULTS: We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants).

    AUTHORS' CONCLUSIONS: We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.

    Matched MeSH terms: Randomized Controlled Trials as Topic/statistics & numerical data
  5. Chan SP, Colagiuri S
    Diabetes Res Clin Pract, 2015 Oct;110(1):75-81.
    PMID: 26361859 DOI: 10.1016/j.diabres.2015.07.002
    AIMS: Sulfonylureas are well positioned in treating type 2 diabetes, after lifestyle modification and metformin. The sulfonylurea gliclazide was given preference over glibenclamide in older people with type 2 diabetes in the World Health Organization model list of essential medicines. Consequently, a systematic review and meta-analysis of randomized controlled trials of the efficacy and safety of gliclazide versus other oral insulinotropic agents (sulfonylureas, dipeptidyl peptidase-4 inhibitors, and glinides) was performed.

    METHODS: Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas.

    RESULTS: Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%).

    CONCLUSION: Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.

    Matched MeSH terms: Randomized Controlled Trials as Topic/statistics & numerical data
  6. Voon HY, Shafie AA, Bujang MA, Suharjono HN
    J Obstet Gynaecol Res, 2018 Jan;44(1):109-116.
    PMID: 29027315 DOI: 10.1111/jog.13486
    AIM: To evaluate the cost effectiveness of carbetocin compared to oxytocin when used as prophylaxis against post-partum hemorrhage (PPH) during cesarean deliveries.

    METHODS: A systematic review of the literature was performed to identify randomized controlled trials that compared the use of carbetocin to oxytocin in the context of cesarean deliveries. Cost effectiveness analysis was then performed using secondary data from the perspective of a maternity unit within the Malaysian Ministry of Health, over a 24 h time period.

    RESULTS: Seven randomized controlled trials with over 2000 patients comparing carbetocin with oxytocin during cesarean section were identified. The use of carbetocin in our center, which has an average of 3000 cesarean deliveries annually, would have prevented 108 episodes of PPH, 104 episodes of transfusion and reduced the need for additional uterotonics in 455 patients. The incremental cost effectiveness ratio of carbetocin for averting an episode of PPH was US$278.70.

    CONCLUSION: Reduction in retreatment, staffing requirements, transfusion and potential medication errors mitigates the higher index cost of carbetocin. From a pharmacoeconomic perspective, in the context of cesarean section, carbetocin was cost effective as prophylaxis against PPH. Ultimately, the relative value placed on the outcomes above and the individual unit's resources would influence the choice of uterotonic.

    Matched MeSH terms: Randomized Controlled Trials as Topic/statistics & numerical data*
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