-
1.
Anti-vascular endothelial growth factor therapy and retinal non-perfusion in diabetic retinopathy: A meta-analysis of randomised trials.
Nanji, K, Sarohia, GS, Xie, J, Patil, NS, Phillips, M, Zeraatkar, D, Thabane, L, Guymer, RH, Kaiser, PK, Sivaprasad, S, et al
Acta ophthalmologica. 2024;(1):e31-e41
Abstract
PURPOSE Retinal non-perfusion (RNP) is fundamental to disease onset and progression in diabetic retinopathy (DR). Whether anti-vascular endothelial growth factor (anti-VEGF) therapy can modify RNP progression is unclear. This investigation quantified the impact of anti-VEGF therapy on RNP progression compared with laser or sham at 12 months. METHODS A systematic review and meta-analysis of randomised controlled trials (RCTs) were performed; Ovid MEDLINE, EMBASE and CENTRAL were searched from inception to 4th March 2022. The change in any continuous measure of RNP at 12 months and 24 months was the primary and secondary outcomes, respectively. Outcomes were reported utilising standardised mean differences (SMD). The Cochrane Risk of Bias Tool version-2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines informed risk of bias and certainty of evidence assessments. RESULTS Six RCTs (1296 eyes) and three RCTs (1131 eyes) were included at 12 and 24 months, respectively. Meta-analysis demonstrated that RNP progression may be slowed with anti-VEGF therapy compared with laser/sham at 12 months (SMD: -0.17; 95% confidence interval [CI]: -0.29, -0.06; p = 0.003; I2 = 0; GRADE rating: LOW) and 24-months (SMD: -0.21; 95% CI: -0.37, -0.05; p = 0.009; I2 = 28%; GRADE rating: LOW). The certainty of evidence was downgraded due to indirectness and due to imprecision. CONCLUSION Anti-VEGF treatment may slightly impact the pathophysiologic process of progressive RNP in DR. The dosing regimen and the absence of diabetic macular edema may impact this potential effect. Future trials are needed to increase the precision of the effect and inform the association between RNP progression and clinically important events. PROSPERO REGISTRATION CRD42022314418.
-
2.
Detailed statistical analysis plan for a secondary Bayesian analysis of the SafeBoosC-III trial: a multinational, randomised clinical trial assessing treatment guided by cerebral oximetry monitoring versus usual care in extremely preterm infants.
Olsen, MH, Hansen, ML, Lange, T, Gluud, C, Thabane, L, Greisen, G, Jakobsen, JC, ,
Trials. 2023;(1):737
Abstract
BACKGROUND Extremely preterm infants have a high mortality and morbidity. Here, we present a statistical analysis plan for secondary Bayesian analyses of the pragmatic, sufficiently powered multinational, trial-SafeBoosC III-evaluating the benefits and harms of cerebral oximetry monitoring plus a treatment guideline versus usual care for such infants. METHODS The SafeBoosC-III trial is an investigator-initiated, open-label, randomised, multinational, pragmatic, phase III clinical trial with a parallel-group design. The trial randomised 1601 infants, and the frequentist analyses were published in April 2023. The primary outcome is a dichotomous composite outcome of death or severe brain injury. The exploratory outcomes are major neonatal morbidities associated with neurodevelopmental impairment later in life: (1) bronchopulmonary dysplasia; (2) retinopathy of prematurity; (3) late-onset sepsis; (4) necrotising enterocolitis; and (5) number of major neonatal morbidities (count of bronchopulmonary dysplasia, retinopathy of prematurity, and severe brain injury). The primary Bayesian analyses will use non-informed priors including all plausible effects. The models will use a Hamiltonian Monte Carlo sampler with 1 chain, a sampling of 10,000, and at least 25,000 iterations for the burn-in period. In Bayesian statistics, such analyses are referred to as 'posteriors' and will be presented as point estimates with 95% credibility intervals (CrIs), encompassing the most probable results based on the data, model, and priors selected. The results will be presented as probability of any benefit or any harm, Bayes factor, and the probability of clinical important benefit or harm. Two statisticians will analyse the blinded data independently following this protocol. DISCUSSION This statistical analysis plan presents a secondary Bayesian analysis of the SafeBoosC-III trial. The analysis and the final manuscript will be carried out and written after we publicise the primary frequentist trial report. Thus, we can interpret the findings from both the frequentists and Bayesian perspective. This approach should provide a better foundation for interpreting of our findings. TRIAL REGISTRATION ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.
-
3.
Mobile phone text messaging plus motivational interviewing versus usual care: study protocol for a randomized controlled trial to evaluate effects on breastfeeding, child health, and survival outcomes, among women living with HIV (MTI-MI).
Zunza, M, Thabane, L, Kuhn, L, Els, C, Cotton, MF, Young, T
Trials. 2023;(1):639
Abstract
BACKGROUND Many infants in low-resourced settings at high risk of infectious disease morbidity and death are deprived of the immunological and nutritional benefits of breast milk, through an attenuated duration of breast milk exposure. South Africa has one of the lowest exclusive breastfeeding rates in Africa, with 8% of infants under 6 months of age. We assume that breastfeeding is sustained among women living with HIV receiving weekly text messages and motivational interviewing and that this contributes to improved infant health outcomes. OBJECTIVES (1) To evaluate the effectiveness of a combined intervention of mobile phone text messaging and motivational interviewing in promoting (a) exclusive breastfeeding and (b) any form of breastfeeding, until 6 months of child age, compared to usual care, among mothers living with HIV. (2) To evaluate the effectiveness of a combined intervention on (a) reduction in all-cause hospitalization and mortality rates and (b) improvements in infant linear growth, compared to usual care, among HIV-exposed infants aged 0-6 months. METHODS We are conducting a clinical trial to determine whether text messaging plus motivational interviewing prolongs breastfeeding and improves infant health outcomes. We are recruiting 275 women living with HIV and their HIV-exposed infants at birth and randomly assign study interventions for 6 months. STATISTICAL METHODS Breastfeeding rates are compared between the study groups using a standard proportion test and binomial regression. Survival endpoints are presented using Kaplan-Meier survival curves and compared between the study groups using the Cox proportional-hazards regression model. The count endpoint is analysed using the Poisson random-effects model and mean cumulative function. We use mixed linear regression models to assess the evolution of infant growth over time. The maximum likelihood method will be used to handle missing data. DISCUSSION The study findings may facilitate decision-making on (1) whether implementation of the breastfeeding policy achieved the desired outcomes, (2) interventions needed to sustain breastfeeding, and (3) whether the interventions do have an impact on child health. TRIAL REGISTRATION ClinicalTrials.gov NCT05063240. Pan African Clinical Trial Registry PACTR202110870407786. Oct. 1, 2021.
-
4.
Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.
Slobogean, GP, Bzovsky, S, O'Hara, NN, Marchand, LS, Hannan, ZD, Demyanovich, HK, Connelly, DW, Adachi, JD, Thabane, L, Sprague, S
JBMR plus. 2023;7(1):e10705
-
-
-
-
Free full text
Plain language summary
Almost half of all adult patients with fractures are vitamin D deficient. The aim of this double-blind, randomised, placebo-controlled trial was to evaluate the efficacy of different vitamin D regimens on the healing of acute tibia and femur fractures. 102 18-50-year-old patients were enrolled in the study and randomised to receive a) two high doses (150,000 IU) at time of injury and after 6 weeks, b) 4000 IU daily, c) 600 IU daily or d) placebo for 3 months. After 3 months, there were no statistically significant differences between the 3 intervention groups with respect to clinical or radiographic outcomes of fracture healing. The authors report a significantly better clinical, but not radiographic, outcome for 4000 IU per day versus placebo with a p-value of 0.15 (note: generally, to be considered statistically significant, p should be < 0.05). Similar results were observed after 12 months. There was no significant correlation between vitamin D levels and fracture healing. The authors concluded that high dose vitamin D may confer a modest benefit for fracture healing but that this requires confirmation from a larger clinical trial.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The evidence base for the use of vitamin D supplements in isolation to support fracture healing is weak.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
- Low levels of vitamin D can have negative effects on bone metabolism and healing of fractures
- Almost half of all adult fracture patients are vitamin D deficient
- The aim of this study was to evaluate the effectiveness of supplementing vitamin D3 (VD3) to improve tibia and femur fracture healing.
Methods
- Four-arm, double-blind, randomised, phase II screening, placebo-controlled trial
- 102 adult patients (aged 18-50 years) with a non-osteoporotic tibial or femoral shaft fracture were randomised into 1 of 4 treatment groups
- Just over half (56%) of participants were vitamin D3 deficient at baseline
- Intervention groups: 1) 150,000 IU VD3 loading dose at injury and at 6 weeks (high loading) plus daily placebo; 2) placebo loading doses plus 4000 IU VD3 daily (high dose); 3) placebo loading doses plus 600 IU VD3 daily (low dose); 4) placebo loading dose plus placebo daily
- Duration: 3 months intervention, further 9 months follow-up. Vitamin D levels were assessed at 6 weeks and 3 months.
Primary outcome measures at 3 months:
- Clinical assessment using the Function IndeX for Trauma (FIX-IT)
- Radiographic assessment using the Radiographic Union Score for Tibial fractures (RUST).
Secondary outcomes: as above at 6, 9 and 12 months.
Results at 3 months:
- No statistically significant difference between high loading and high dose, high and low dose or low dose and placebo for either clinical or radiological assessment (all p-values ≥0.4)
- Post-hoc analysis of any dose vs placebo showed no significant difference with either clinical or radiological assessment (all p-values ≥0.25)
- Post-hoc analysis of high dose vs placebo showed no significant difference for radiological assessment (p=0.76) whilst it was reported as statistically significant for clinical assessment with p=0.16, with a benefit of VD3 supplementation.
- Similar results were seen at 12 months with reported benefit of high dose VD3 for fracture healing with p=0.18
- Vitamin D levels improved in all 3 VD3 groups from baseline to 6 weeks
- There was no statistically significant correlation between fracture healing and vitamin D level.
Conclusion
The authors conclude that VD3 supplementation may be of modest benefit for fracture healing, but further, larger trials are needed to confirm this.
Clinical practice applications:
- When working with clients who present with a fracture, it should be noted that the evidence for benefit of vitamin D supplementation alone for fracture healing is weak.
Considerations for future research:
- Larger studies to increase the statistical power to detect smaller benefits are required
- Larger studies may also identify differences in potential benefits between patient populations with different baseline levels of vitamin D.
Abstract
Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
-
5.
Role of anti-vascular endothelial growth factor in the management of non-proliferative diabetic retinopathy without centre-involving diabetic macular oedema: a meta-analysis of trials.
Chaudhary, V, Sarohia, GS, Phillips, MR, Park, D, Xie, J, Zeraatkar, D, Fung, M, Thabane, L, Loewenstein, A, Holz, FG, et al
Eye (London, England). 2023;(10):1966-1974
Abstract
This systematic review and meta-analysis investigated the impact of anti-vascular endothelial growth factor (VEGF) treatment in management of eyes with non-proliferative diabetic retinopathy (NPDR) without centre involving diabetic macular oedema (CI-DMO). We searched multiple databases for all randomised clinical trials (RCTs) that evaluated anti-VEGF treatment versus observation in eyes with NPDR without CI-DMO. Data was collected for six outcomes (best corrected visual acuity (BCVA) improvement, diabetic retinopathy severity score (DRSS), central subfield thickness, progression to vision threatening complications (VTCs), ocular adverse events and quality of life measures). Risk of bias was assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2) and certainty of evidence was assessed using Grade of Recommendations, Assessment, Development and Evaluation (GRADE). We identified a total of 2 unique RCTs that compared aflibercept and sham to treat a total of 811 eyes. For BCVA change, there was a small, clinically insignificant benefit for aflibercept treatment at year 2 (MD 0.70, 95% CI 0.02-1.38, GRADE rating: MODERATE). DRSS demonstrated a statistically significant improvement with aflibercept use at year 2 (RR 3.76, 95% CI 2.75-5.13, GRADE rating: MODERATE). VTCs were significantly less in aflibercept arm at year 2 (RR 0.30, 95% CI 0.23-0.40, GRADE rating: MODERATE). In conclusion, aflibercept treatment versus observation in eyes with NPDR without CI-DMO can result in reduced risk of development of VTCs and regression of DRSS score over 2 years. Future trials are needed to increase the precision of the treatment effect and to provide data on quality-of-life metrics.PROSPERO Registration: CRD42021288608.
-
6.
Obesity as an independent risk factor for COVID-19 severity and mortality.
Tadayon Najafabadi, B, Rayner, DG, Shokraee, K, Shokraie, K, Panahi, P, Rastgou, P, Seirafianpour, F, Momeni Landi, F, Alinia, P, Parnianfard, N, et al
The Cochrane database of systematic reviews. 2023;(5):CD015201
Abstract
BACKGROUND Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate. DATA COLLECTION AND ANALYSIS Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis. MAIN RESULTS We identified 171 studies, 149 of which were included in meta-analyses. As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.
-
7.
Saturated fat, the estimated absolute risk and certainty of risk for mortality and major cancer and cardiometabolic outcomes: an overview of systematic reviews.
Talukdar, JR, Steen, JP, Goldenberg, JZ, Zhang, Q, Vernooij, RWM, Ge, L, Zeraatkar, D, Bała, MM, Ball, GDC, Thabane, L, et al
Systematic reviews. 2023;(1):179
Abstract
OBJECTIVE To assess the impact of reducing saturated fat or fatty foods, or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of mortality and major cancer and cardiometabolic outcomes in adults. METHODS We searched MEDLINE, EMBASE, CINAHL, and references of included studies for systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs) and observational studies in adults published in the past 10 years. Eligible reviews investigated reducing saturated fat or fatty foods or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of cancer and cardiometabolic outcomes and assessed the certainty of evidence for each outcome using, for example, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. We assessed the quality of SRMAs using a modified version of AMSTAR-2. Results were summarized as absolute estimates of effect together with the certainty of effects using a narrative synthesis approach. RESULTS We included 17 SRMAs (13 reviews of observational studies with follow-up 1 to 34 years; 4 reviews of RCTs with follow-up 1 to 17 years). The quality of two-thirds of the SRMAs was critically low to moderate; the main limitations included deficient reporting of study selection, absolute effect estimates, sources of funding, and a priori subgroups to explore heterogeneity. Our included reviews reported > 100 estimates of effect across 11 critically important cancer and cardiometabolic outcomes. High quality SRMAs consistently and predominantly reported low to very low certainty evidence that reducing or replacing saturated fat was associated with a very small risk reduction in cancer and cardiometabolic endpoints. The risk reductions where approximately divided, some being statistically significant and some being not statistically significant. However, based on 2 moderate to high quality reviews, we found moderate certainty evidence for a small but important effect that was statistically significant for two outcomes (total mortality events [20 fewer events per 1000 followed] and combined cardiovascular events [16 fewer per 1000 followed]). Conversely, 4 moderate to high quality reviews showed very small effects on total mortality, with 3 of these reviews showing non-statistically significant mortality effects. CONCLUSION Systematic reviews investigating the impact of SFA on mortality and major cancer and cardiometabolic outcomes almost universally suggest very small absolute changes in risk, and the data is based primarily on low and very low certainty evidence. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020172141.
-
8.
Global Prevalence of Diabetic Retinopathy in Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis.
Cioana, M, Deng, J, Nadarajah, A, Hou, M, Qiu, Y, Chen, SSJ, Rivas, A, Toor, PP, Banfield, L, Thabane, L, et al
JAMA network open. 2023;(3):e231887
-
-
Free full text
-
Abstract
IMPORTANCE Type 2 diabetes (T2D) is increasing globally. Diabetic retinopathy (DR) is a leading cause of blindness in adults with T2D; however, the global burden of DR in pediatric T2D is unknown. This knowledge can inform retinopathy screening and treatments to preserve vision in this population. OBJECTIVE To estimate the global prevalence of DR in pediatric T2D. DATA SOURCES MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, the Web of Science, and the gray literature (ie, literature containing information that is not available through traditional publishing and distribution channels) were searched for relevant records from the date of database inception to April 4, 2021, with updated searches conducted on May 17, 2022. Searches were limited to human studies. No language restrictions were applied. Search terms included diabetic retinopathy; diabetes mellitus, type 2; prevalence studies; and child, adolescent, teenage, youth, and pediatric. STUDY SELECTION Three teams, each with 2 reviewers, independently screened for observational studies with 10 or more participants that reported the prevalence of DR. Among 1989 screened articles, 27 studies met the inclusion criteria for the pooled analysis. DATA EXTRACTION AND SYNTHESIS This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines for systematic reviews and meta-analyses. Two independent reviewers performed the risk of bias and level of evidence analyses. The results were pooled using a random-effects model, and heterogeneity was reported using χ2 and I2 statistics. MAIN OUTCOMES AND MEASURES The main outcome was the estimated pooled global prevalence of DR in pediatric T2D. Other outcomes included DR severity and current DR assessment methods. The association of diabetes duration, sex, race, age, and obesity with DR prevalence was also assessed. RESULTS Among the 27 studies included in the pooled analysis (5924 unique patients; age range at T2D diagnosis, 6.5-21.0 years), the global prevalence of DR in pediatric T2D was 6.99% (95% CI, 3.75%-11.00%; I2 = 95%; 615 patients). Fundoscopy was less sensitive than 7-field stereoscopic fundus photography in detecting retinopathy (0.47% [95% CI, 0%-3.30%; I2 = 0%] vs 13.55% [95% CI, 5.43%-24.29%; I2 = 92%]). The prevalence of DR increased over time and was 1.11% (95% CI, 0.04%-3.06%; I2 = 5%) at less than 2.5 years after T2D diagnosis, 9.04% (95% CI, 2.24%-19.55%; I2 = 88%) at 2.5 to 5.0 years after T2D diagnosis, and 28.14% (95% CI, 12.84%-46.45%; I2 = 96%) at more than 5 years after T2D diagnosis. The prevalence of DR increased with age, and no differences were noted based on sex, race, or obesity. Heterogeneity was high among studies. CONCLUSIONS AND RELEVANCE In this study, DR prevalence in pediatric T2D increased significantly at more than 5 years after diagnosis. These findings suggest that retinal microvasculature is an early target of T2D in children and adolescents, and annual screening with fundus photography beginning at diagnosis offers the best assessment method for early detection of DR in pediatric patients.
-
9.
Intravenous ketorolac versus morphine in children presenting with suspected appendicitis: a pilot single-centre non-inferiority randomised controlled trial.
Eltorki, M, Busse, JW, Freedman, SB, Thompson, G, Beattie, K, Serbanescu, C, Carciumaru, R, Thabane, L, Ali, S
BMJ open. 2022;(4):e056499
Abstract
OBJECTIVES Despite a lack of evidence demonstrating superiority to non-steroidal anti-inflammatory drugs, like ketorolac, that are associated with lower risk of harms, opioids remain the most prescribed analgesic for acute abdominal pain. In this pilot trial, we will assess the feasibility of a definitive trial comparing ketorolac with morphine in children with suspected appendicitis. We hypothesise that our study will be feasible based on a 40% consent rate. METHODS AND ANALYSIS A single-centre, non-inferiority, blinded (participant, clinician, investigators and outcome assessors), double-dummy randomised controlled trial of children aged 6-17 years presenting to a paediatric emergency department with ≤5 days of moderate to severe abdominal pain (≥5 on a Verbal Numerical Rating Scale) and are investigated for appendicitis. We will use variable randomised blocks of 4-6 and allocate participants in 1:1 ratio to receive either intravenous (IV) ketorolac 0.5 mg/kg+IV morphine placebo or IV morphine 0.1 mg/kg+IV ketorolac placebo. Analgesic co-intervention will be limited to acetaminophen (commonly used as first-line therapy). Participants in both groups will be allowed rescue therapy (morphine 0.5 mg/kg) within 60 min of our intervention. Our primary feasibility outcome is the proportion of eligible patients approached who provide informed consent and are enrolled in our trial. Our threshold for feasibility will be to achieve a ≥40% consent rate, and we will enrol 100 participants into our pilot trial. ETHICS AND DISSEMINATION Our study has received full approval by the Hamilton integrated Research Ethics Board. We will disseminate our study findings at national and international paediatric research conferences to garner interest and engage sites for a future multicentre definitive trial. TRIAL REGISTRATION NCT04528563, Pre-results.
-
10.
Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Sharif, S, Greer, A, Skorupski, C, Hao, Q, Johnstone, J, Dionne, JC, Lau, V, Manzanares, W, Eltorki, M, Duan, E, et al
Critical care medicine. 2022;(8):1175-1186
Abstract
OBJECTIVES To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children. DATA SOURCES We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021. STUDY SELECTION We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate. DATA EXTRACTION Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7-10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55-0.89; RD, 5.5% reduction; 95% CI, 8.2-2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57-2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18-3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31-3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87-1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS. CONCLUSIONS Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.