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Understanding effect size: an international online survey among psychiatrists, psychologists, physicians from other medical specialities, dentists and other health professionals.
Heimke, F, Furukawa, Y, Siafis, S, Johnston, BC, Engel, RR, Furukawa, TA, Leucht, S
BMJ mental health. 2024;(1)
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Abstract
BACKGROUND AND OBJECTIVE Various ways exist to display the effectiveness of medical treatment options. This study examined various psychiatric, medical and allied professionals' understanding and perceived usefulness of eight effect size indices for presenting both dichotomous and continuous outcome data. METHODS We surveyed 1316 participants from 13 countries using an online questionnaire. We presented hypothetical treatment effects of interventions versus placebo concerning chronic pain using eight different effect size measures. For each index, the participants had to judge the magnitude of the shown effect, to indicate how certain they felt about their own answer and how useful they found the given effect size index. FINDINGS Overall, 762 (57.9%) participants fully completed the questionnaire. In terms of understanding, the best results emerged when both the control event rate (CER) and the experimental event rate (EER) were presented. The difference in minimal importance difference units (MID unit) was understood worst. Respondents also found CER and EER to be the most useful presentation approach while they rated MID unit as the least useful. Confidence in the risk ratio ranked high, even though it was rather poorly understood. CONCLUSIONS AND CLINICAL IMPLICATIONS For dichotomous outcomes, presenting the effects in terms of the CER and EER could lead to the most correct interpretation. Relative measures including the risk ratio must be supplemented with absolute measures such as the CER and EER. Effects on continuous outcomes were better understood through standardised mean differences than mean differences. These can also be supplemented by dichotomised CER and EER.
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Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in extremely preterm infants: a clinical practice guideline incorporating family values and preferences.
Mitra, S, Whitehead, L, Smith, K, Maclean, B, Nixon, R, Veysey, A, Campbell-Yeo, M, Kuhle, S, Gale, C, Soll, R, et al
Archives of disease in childhood. Fetal and neonatal edition. 2024;(3):232-238
Abstract
ImportanceProphylactic cyclo-oxygenase inhibitors (COX-Is) such as indomethacin, ibuprofen and acetaminophen may prevent morbidity and mortality in extremely preterm infants (born ≤28 weeks' gestation). However, there is controversy around which COX-I, if any, is the most effective and safest, which has resulted in considerable variability in clinical practice. Our objective was to develop rigorous and transparent clinical practice guideline recommendations for the prophylactic use of COX-I drugs for the prevention of mortality and morbidity in extremely preterm infants. The Grading of Recommendations Assessment, Development and Evaluation evidence-to-decision framework for multiple comparisons was used to develop the guideline recommendations. A 12-member panel, including 5 experienced neonatal care providers, 2 methods experts, 1 pharmacist, 2 parents of former extremely preterm infants and 2 adults born extremely preterm, was convened. A rating of the most important clinical outcomes was established a priori. Evidence from a Cochrane network meta-analysis and a cross-sectional mixed-methods study exploring family values and preferences were used as the primary sources of evidence. The panel recommended that prophylaxis with intravenous indomethacin may be considered in extremely preterm infants (conditional recommendation, moderate certainty in estimate of effects). Shared decision making with parents was encouraged to evaluate their values and preferences prior to therapy. The panel recommended against routine use of ibuprofen prophylaxis in this gestational age group (conditional recommendation, low certainty in the estimate of effects). The panel strongly recommended against use of prophylactic acetaminophen (strong recommendation, very low certainty in estimate of effects) until further research evidence is available.
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Microbiota signatures and mucosal healing in the use of enteral nutrition therapy v. corticosteroids for the treatment of children with Crohn's disease: a systematic review and meta-analysis.
Ding, Z, Ninan, K, Johnston, BC, Moayyedi, P, Sherlock, M, Zachos, M
The British journal of nutrition. 2023;(8):1385-1402
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Abstract
Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN v. CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD. Three RCT (n 76) and sixteen cohort studies (n 1104) compared EEN v. CS. With limited available data (one RCT), the effect on intestinal microbiome indicated a trend towards EEN regarding Shannon diversity. Based on two RCT, EEN achieved higher mucosal healing than CS (risk ratio (RR) 2·36, 95 % CI (1·22, 4·57), low certainty). Compared with CS, patients on EEN were less likely to experience adverse events based on two RCT (RR 0·32, 95 % CI (0·13, 0·80), low certainty). For HRQL, there was a trend in favour of CS based on data from two published abstracts of cohort studies. Based on thirteen cohort studies, EEN achieved higher clinical remission than CS (RR 1·18, 95 % CI (1·02, 1·38), very low certainty). Studies also reported no important differences in relapse and adherence. Compared with CS, EEN may improve mucosal healing with fewer adverse events based on RCT data. While limited data indicate the need for further trials, this is the first systematic review to comprehensively summarise the data on intestinal microbiome, mucosal healing and HRQOL when comparing enteral nutrition and CS in paediatric CD.
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Incorporation of patient and family values and preferences for health-related outcomes in paediatric obesity management: A systematic review.
Zenlea, IS, Sebastianski, M, Kucera, M, Mushquash, AR, Boles, K, Brogly, J, Delacruz, B, McGeown, L, Ball, GDC, Johnston, BC, et al
Pediatric obesity. 2023;(5):e13006
Abstract
OBJECTIVE A systematic review of value and preference studies conducted in children and their caregivers related to the estimated benefits and harms of interventions for managing paediatric obesity. METHODS We searched Ovid Medline (1946-2022), Ovid Embase (1974-2022), EBSCO CINAHL (inception to 2022), Elsevier Scopus (inception to 2022), and ProQuest Dissertations & Theses (inception to 2022). Reports were eligible if they included: behavioural and psychological, pharmacological, or surgical interventions; participants between (or had a mean age within) 0-18 years old with overweight or obesity; systematic reviews, primary quantitative, qualitative, or mixed/multiple methods studies; and values and preferences as main study outcomes. At least two team members independently screened studies, abstracted data, and appraised study quality. RESULTS Our search yielded 11 010 reports; eight met the inclusion criteria. One study directly assessed values and preferences based on hypothetical pharmacological treatment for hyperphagia in individuals with Prader-Willi Syndrome. Although not having reported on values and preferences using our a priori definitions, the remaining seven qualitative studies (n = 6 surgical; n = 1 pharmacological) explored general beliefs, attitudes, and perceptions about surgical and pharmacological interventions. No studies pertained to behavioural and psychological interventions. CONCLUSION Future research is needed to elicit the values and preferences of children and caregivers using the best available estimates of the benefits and harms for pharmacological, surgical, and behavioural and psychological interventions.
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Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis.
Karam, G, Agarwal, A, Sadeghirad, B, Jalink, M, Hitchcock, CL, Ge, L, Kiflen, R, Ahmed, W, Zea, AM, Milenkovic, J, et al
BMJ (Clinical research ed.). 2023;:e072003
Abstract
OBJECTIVE To determine the relative efficacy of structured named diet and health behaviour programmes (dietary programmes) for prevention of mortality and major cardiovascular events in patients at increased risk of cardiovascular disease. DESIGN Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES AMED (Allied and Complementary Medicine Database), CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ClinicalTrials.gov were searched up to September 2021. STUDY SELECTION Randomised trials of patients at increased risk of cardiovascular disease that compared dietary programmes with minimal intervention (eg, healthy diet brochure) or alternative programmes with at least nine months of follow-up and reporting on mortality or major cardiovascular events (such as stroke or non-fatal myocardial infarction). In addition to dietary intervention, dietary programmes could also include exercise, behavioural support, and other secondary interventions such as drug treatment. OUTCOMES AND MEASURES All cause mortality, cardiovascular mortality, and individual cardiovascular events (stroke, non-fatal myocardial infarction, and unplanned cardiovascular interventions). REVIEW METHODS Pairs of reviewers independently extracted data and assessed risk of bias. A random effects network meta-analysis was performed using a frequentist approach and grading of recommendations assessment, development and evaluation (GRADE) methods to determine the certainty of evidence for each outcome. RESULTS 40 eligible trials were identified with 35 548 participants across seven named dietary programmes (low fat, 18 studies; Mediterranean, 12; very low fat, 6; modified fat, 4; combined low fat and low sodium, 3; Ornish, 3; Pritikin, 1). At last reported follow-up, based on moderate certainty evidence, Mediterranean dietary programmes proved superior to minimal intervention for the prevention of all cause mortality (odds ratio 0.72, 95% confidence interval 0.56 to 0.92; patients at intermediate risk: risk difference 17 fewer per 1000 followed over five years), cardiovascular mortality (0.55, 0.39 to 0.78; 13 fewer per 1000), stroke (0.65, 0.46 to 0.93; 7 fewer per 1000), and non-fatal myocardial infarction (0.48, 0.36 to 0.65; 17 fewer per 1000). Based on moderate certainty evidence, low fat programmes proved superior to minimal intervention for prevention of all cause mortality (0.84, 0.74 to 0.95; 9 fewer per 1000) and non-fatal myocardial infarction (0.77, 0.61 to 0.96; 7 fewer per 1000). The absolute effects for both dietary programmes were more pronounced for patients at high risk. There were no convincing differences between Mediterranean and low fat programmes for mortality or non-fatal myocardial infarction. The five remaining dietary programmes generally had little or no benefit compared with minimal intervention typically based on low to moderate certainty evidence. CONCLUSIONS Moderate certainty evidence shows that programmes promoting Mediterranean and low fat diets, with or without physical activity or other interventions, reduce all cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. Mediterranean programmes are also likely to reduce stroke risk. Generally, other named dietary programmes were not superior to minimal intervention. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016047939.
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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.
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Updating the Canadian clinical practice guideline for managing pediatric obesity: a protocol.
Johnston, BC, Merdad, R, Sherifali, D, Kebbe, M, Birken, CS, Buchholz, A, Ge, L, Gehring, ND, Hadjiyannakis, S, Hamilton, J, et al
CMAJ open. 2022;(1):E155-E164
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Abstract
BACKGROUND Since the first national guideline for managing obesity in adults and children in Canada was published in 2007, new evidence has emerged and guideline standards have evolved. Our purpose is to describe the protocol used to update the Canadian clinical practice guideline for managing pediatric obesity. METHODS This guideline will update the pediatric components of the 2007 Canadian clinical practice guideline for the management of obesity. In partnership with Obesity Canada, we began preliminary work in 2019; activities are scheduled for completion in 2022. The guideline will follow standards developed by the National Academy of Medicine and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Guideline development will be informed by 5 complementary literature reviews: a scoping review that focuses on clinical assessment in pediatric obesity management and 4 systematic reviews to synthesize evidence regarding families' values and preferences as well as the safety and effectiveness of interventions (psychological and behavioural; pharmacotherapeutic; and surgical). We will use standard systematic review methodology, including summarizing and assessing the certainty of evidence and determining the strength of recommendations. Competing interests will be managed proactively according to recommendations from the Guidelines International Network. Diverse stakeholders, including families and clinicians, will be engaged throughout guideline development. INTERPRETATION The guideline will support Canadian families and clinicians to make informed, value-sensitive and evidence-based clinical decisions related to managing pediatric obesity. The guideline and accompanying resources for end-users will be published in English and French, and we will partner with Obesity Canada to optimize dissemination using integrated and end-of-project knowledge translation.
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Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis.
Mitra, S, Gardner, CE, MacLellan, A, Disher, T, Styranko, DM, Campbell-Yeo, M, Kuhle, S, Johnston, BC, Dorling, J
The Cochrane database of systematic reviews. 2022;(4):CD013846
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Abstract
BACKGROUND Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Cyclooxygenase inhibitors (COX-I) may prevent PDA-related complications. Controversy exists on which COX-I drug is the most effective and has the best safety profile in preterm infants. OBJECTIVES To compare the effectiveness and safety of prophylactic COX-I drugs and 'no COXI prophylaxis' in preterm infants using a Bayesian network meta-analysis (NMA). SEARCH METHODS Searches of Cochrane CENTRAL via Wiley, OVID MEDLINE and Embase via Elsevier were conducted on 9 December 2021. We conducted independent searches of clinical trial registries and conference abstracts; and scanned the reference lists of included trials and related systematic reviews. SELECTION CRITERIA We included randomised controlled trials (RCTs) that enrolled preterm or low birth weight infants within the first 72 hours of birth without a prior clinical or echocardiographic diagnosis of PDA and compared prophylactic administration of indomethacin or ibuprofen or acetaminophen versus each other, placebo or no treatment. DATA COLLECTION AND ANALYSIS We used the standard methods of Cochrane Neonatal. We used the GRADE NMA approach to assess the certainty of evidence derived from the NMA for the following outcomes: severe intraventricular haemorrhage (IVH), mortality, surgical or interventional PDA closure, necrotizing enterocolitis (NEC), gastrointestinal perforation, chronic lung disease (CLD) and cerebral palsy (CP). MAIN RESULTS We included 28 RCTs (3999 preterm infants). Nineteen RCTs (n = 2877) compared prophylactic indomethacin versus placebo/no treatment, 7 RCTs (n = 914) compared prophylactic ibuprofen versus placebo/no treatment and 2 RCTs (n = 208) compared prophylactic acetaminophen versus placebo/no treatment. Nine RCTs were judged to have high risk of bias in one or more domains.We identified two ongoing trials on prophylactic acetaminophen. Bayesian random-effects NMA demonstrated that prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; absolute risk difference [ARD] 43 fewer [95% CrI, 65 fewer to 16 fewer] per 1000; median rank 2, 95% CrI 1-3; moderate-certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; ARD 24 fewer [95% CrI, 58 fewer to 16 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and surgical PDA closure (network RR 0.40, 95% CrI 0.14 to 0.66; ARD 52 fewer [95% CrI, 75 fewer to 30 fewer] per 1000; median rank 2, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic indomethacin resulted in trivial difference in NEC (network RR 0.76, 95% CrI 0.35 to 1.2; ARD 16 fewer [95% CrI, 42 fewer to 13 more] per 1000; median rank 2, 95% CrI 1-3; high-certainty), gastrointestinal perforation (network RR 0.92, 95% CrI 0.11 to 3.9; ARD 4 fewer [95% CrI, 42 fewer to 137 more] per 1000; median rank 1, 95% CrI 1-3; moderate-certainty) or CP (network RR 0.97, 95% CrI 0.44 to 2.1; ARD 3 fewer [95% CrI, 62 fewer to 121 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty) and may result in a small increase in CLD (network RR 1.10, 95% CrI 0.93 to 1.3; ARD 36 more [95% CrI, 25 fewer to 108 more] per 1000; median rank 3, 95% CrI 1-3; low-certainty). Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; ARD 39 fewer [95% CrI, 75 fewer to 18 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; ARD 66 fewer [95% CrI, from 82 fewer to 31 fewer] per 1000; median rank 1, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic ibuprofen may result in moderate reduction in mortality (network RR 0.83, 95% CrI 0.57 to 1.2; ARD 27 fewer [95% CrI, from 69 fewer to 32 more] per 1000; median rank 2, 95% CrI 1-4; low-certainty) and leads to trivial difference in NEC (network RR 0.73, 95% CrI 0.31 to 1.4; ARD 18 fewer [95% CrI, from 45 fewer to 26 more] per 1000; median rank 1, 95% CrI 1-3; high-certainty), or CLD (network RR 1.00, 95% CrI 0.83 to 1.3; ARD 0 fewer [95% CrI, from 61 fewer to 108 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty). The evidence is very uncertain on effect of ibuprofen on gastrointestinal perforation (network RR 2.6, 95% CrI 0.42 to 20.0; ARD 76 more [95% CrI, from 27 fewer to 897 more] per 1000; median rank 3, 95% CrI 1-3; very low-certainty). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; ARD 22 more [95% CrI, from 122 fewer to 1000 more] per 1000; median rank 4, 95% CrI 1-4; very low-certainty), mortality (network RR 0.49, 95% CrI 0.16 to 1.4; ARD 82 fewer [95% CrI, from 135 fewer to 64 more] per 1000; median rank 1, 95% CrI 1-4; very low-certainty), or CP (network RR 0.36, 95% CrI 0.01 to 6.3; ARD 70 fewer [95% CrI, from 109 fewer to 583 more] per 1000; median rank 1, 95% CrI 1-3; very low-certainty). In summary, based on ranking statistics, both indomethacin and ibuprofen were equally effective (median ranks 2 respectively) in reducing severe IVH and mortality. Ibuprofen (median rank 1) was more effective than indomethacin in reducing surgical PDA ligation (median rank 2). However, no statistically-significant differences were observed between the COX-I drugs for any of the relevant outcomes. AUTHORS' CONCLUSIONS Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate-certainty), may result in a small increase in CLD (low-certainty) and results in trivial differences in NEC (high-certainty), gastrointestinal perforation (moderate-certainty) and cerebral palsy (low-certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate-certainty), may result in a moderate reduction in mortality (low-certainty) and trivial differences in CLD (low-certainty) and NEC (high-certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically-relevant outcomes.
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Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data.
Goldenberg, JZ, Day, A, Brinkworth, GD, Sato, J, Yamada, S, Jönsson, T, Beardsley, J, Johnson, JA, Thabane, L, Johnston, BC
BMJ (Clinical research ed.). 2021;372:m4743
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Plain language summary
Diet modification has long been recognised as a component for the treatment of diabetes. Diets low in carbohydrates have been extensively researched, as a diet for those with Type 2 Diabetes (T2D). This systematic review and meta-analysis aimed to determine the effect of low carbohydrate diets on T2D. The systematic review found 23 studies, including 1357 individuals, investigating the role of low carbohydrate diets on T2D outcomes. Low carbohydrate diet was defined as less than 130g of carbohydrate (less than 26% of calories from carbohydrate) for at least 12 weeks. Results reported at 6 months, found low carbohydrate diets were more effective than a normal diet at achieving diabetes remission. However, this effect diminished at 12 months, although longer term improvements were seen in blood lipids, weight loss and measures of prediabetes. It was concluded that individuals with T2D, eating a low carbohydrate diet for 6 months may reverse the disease. This study could be used by healthcare professionals to recommend a short-term low carbohydrate diet to individuals with T2D, to improve their chance of going into remission.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Type 2 diabetes remains a significant and worsening problem worldwide, despite many pharmaceutical developments and a global emphasis on glycemic control.
- This review highlights structured LCDs as a worthwhile option for the management and treatment of diabetes, providing an opportunity for Nutritional Therapy Practitioners to support clients in adopting evidence-informed, modifiable dietary and lifestyle changes for Type Two Diabetes.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of cases.
- Previous randomised trials assessed low carbohydrate diets (LCDs) (<26-45% of daily calories from carbohydrate) as encouraging to improve blood glucose control and outcomes of type 2 diabetes but did not systematically assessed remission of diabetes using low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes.
- Systematic reviews (SR) and meta-analyses represent the most valuable, reliable, and objective tool to summarise evidence from primary studies.
- This SR assessed 23 randomised controlled trials comparing LCDs with mostly low fat control diets in individuals / subjects / participants with type 2 diabetes. LCDs were defined as diets with less than 130 g/day or less than 26% of calories from carbohydrates, based on 2000 kcal/day. The authors used the Cochrane Risk of Bias tool 2.0 (RoB 2) to assess methodological quality of evidence, GRADE to assess the certainty of evidence
- On the basis of assessment of moderate to low certainty evidence, individuals / subjects / participants adhering to a LCD for six months may experience remission of type 2 diabetes without adverse consequences.
- Primary outcomes of interest were remission of type 2 diabetes (dichotomously defined as HbA1c <6.5% or fasting glucose <7.0 mmol/L), with or without the use of diabetes medication.
- Eight studies reported on remission of diabetes at six months. Pooled analysis showed that when remission was defined by an HbA1c level below 6.5% independent of medication use, LCDs increased remissions by an additional 32 per 100 patients followed (risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264; GRADE=moderate)
- When remission was defined by an HbA1c level below 6.5% and the absence of diabetes medication, LCDs increased remissions at a lower rate (risk difference 0.05, –0.05 to 0.14; 5 studies, n=199; GRADE=low)
- Additional primary outcomes were weight loss, HbA1c:
- 18 studies reported on Weight loss results (mean difference –3.46, 95% confidence interval –5.25 to –1.67; n=882 (note that positive results not sustained at 12 mo)
- Seventeen studies reported on HbA1c levels at six months, LCDs achieved greater reductions in HbA1c than did control diets (mean difference –0.47%, –0.60 to –0.34; n=747
- Limitations of study: 1) the definition of remission of diabetes, 2) Self-reported dietary intake data are prone to measurement error, particularly in dietary trials in which participants are not blinded
- This SR was funded in part by Texas A&M University.
- The authors declared no conflicts of interest.
Clinical practice applications:
The Authors highlight LCD diets incorporating carbohydrate of less than 130 g/day or less than 26% of calories (based on 2000 kcal/day) may be a safe strategy to help individuals with type 2 diabetes achieve weight loss and better blood glucose control over a six-month period. Results may not be sustained at 12 months.
Considerations for future research:
- The definition of diabetes remission needs clarification, especially with regard to threshold concentrations of Hb1Ac or fasting glucose and the use of diabetes medication.
- Safety concerns have been raised with LCDs. Although no significant or clinically important increase in total or serious adverse events was identified in this SR, these outcomes should be reported in future trials to confirm the certainty of evidence for safety.
- The Authors suggest long term, well designed, calorie controlled randomised trials are needed to determine the effects of LCD on sustained weight loss and remission of diabetes.
- Larger treatment effects for LCDs in shorter term trials (3 to <6 months), may be trialed as an effect modifier
Abstract
OBJECTIVE To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN Systematic review and meta-analysis. DATA SOURCES Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020161795.
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Visual Analogue Scale has higher assay sensitivity than WOMAC pain in detecting between-group differences in treatment effects: a meta-epidemiological study.
da Costa, BR, Saadat, P, Basciani, R, Agarwal, A, Johnston, BC, Jüni, P
Osteoarthritis and cartilage. 2021;(3):304-312
Abstract
OBJECTIVE To compare assay sensitivity of the Visual Analogue Scale (VAS) for global osteoarthritis pain and the Western Ontario and McMaster University (WOMAC) pain subscale, and the associated between-trial heterogeneity in effect sizes (ES). DESIGN We included trials with placebo, sham or non-intervention control that included at least 100 patients with hip or knee osteoarthritis per arm, reporting both VAS and WOMAC pain scores. ES were calculated as between-group difference in means divided by the pooled standard deviation and compared using a paired t-test. ES and τ2 as a measure of between-trial heterogeneity were combined using random-effects meta-regression with robust variance estimation to account for the correlation of data within trials and meta-analyses. RESULTS Twenty-eight trials with 44 randomized comparisons were included. In 28 comparisons (64%), ES from VAS favoured the intervention more than those from WOMAC pain (P = 0.003). Twenty-six p-values (59%) were smaller according to VAS (P = 0.008). The 44 comparisons contributed to 12 meta-analyses. Eleven meta-analyses (92%) showed larger benefits of interventions according to VAS, with a combined overall difference in ES of -0.08 (95% CI -0.14 to -0.02). τ2 was similar for VAS and WOMAC pain (difference in τ2, -0.003, 95% CI -0.009 to 0.004). CONCLUSION The VAS for global pain had slightly higher assay sensitivity at trial and meta-analysis levels than the WOMAC pain subscale without relevant increase in between-trial heterogeneity.