Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to ...determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects.
We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.
From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m
; 95% confidence interval CI -1.10 to 0.36;
9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06;
0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.
Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners.
PROSPERO-CRD42015019749.
Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. ...Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness.
A systematic search was conducted to help locate published and unpublished studies. Studies which evaluate teleglaucoma as a screening device for glaucoma were included. A meta-analysis was conducted to provide estimates of diagnostic accuracy, diagnostic odds ratio, and the relative percentage of glaucoma cases detected. The improvements to healthcare service quality and cost data were assessed.
Of 11237 studies reviewed, 45 were included. Our results indicated that, teleglaucoma is more specific and less sensitive than in-person examination. The pooled estimates of sensitivity was 0.832 95% CI 0.770, 0.881 and specificity was 0.790 95% CI 0.668, 0.876. The relative odds of a positive screen test in glaucoma cases are 18.7 times more likely than a negative screen test in a non-glaucoma cases. Additionally, the mean cost for every case of glaucoma detected was $1098.67 US and of teleglaucoma per patient screened was $922.77 US.
Teleglaucoma can accurately discriminate between screen test results with greater odds for positive cases. It detects more cases of glaucoma than in-person examination. Both patients and the healthcare systems benefit from early detection, reduction in wait and travel times, increased specialist referral rates, and cost savings. Teleglaucoma is an effective screening tool for glaucoma specifically for remote and under-services communities.
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Resveratrol for adults with type 2 diabetes mellitus Jeyaraman, Maya M; Al‐Yousif, Nameer S H; Singh Mann, Amrinder ...
Cochrane database of systematic reviews,
01/2020, Volume:
2020, Issue:
1
Journal Article
Peer reviewed
Open access
Background
Type 2 diabetes mellitus (T2DM) is a chronic disorder that is characterised by insulin resistance and hyperglycaemia, which over time may give rise to vascular complications. Resveratrol ...is a plant‐derived nutritional supplement shown to have anti‐diabetic properties in many animal models. Less evidence is available on its safety and efficacy in the management of T2DM in humans.
Objectives
To assess the efficacy and safety of resveratrol formulations for adults with type 2 diabetes mellitus.
Search methods
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and International Pharmaceutical s, as well as the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. The date of the last search was December 2018 for all databases. No language restrictions were applied.
Selection criteria
All randomised controlled trials (RCTs) comparing effects of oral resveratrol (any dose or formulation, duration, or frequency of administration) with placebo, no treatment, other anti‐diabetic medications, or diet or exercise, in adults with a diagnosis of T2DM.
Data collection and analysis
Two review authors independently identified and included RCTs, assessed risk of bias, and extracted study‐level data. Study authors were contacted for any missing information or for clarification of reported data. We assessed studies for certainty of the evidence using the GRADE instrument.
Main results
We identified three RCTs with a total of 50 participants. Oral resveratrol not combined with other plant polyphenols was administered at 10 mg, 150 mg, or 1000 mg daily for a period ranging from four weeks to five weeks. The comparator intervention was placebo. Overall, all three included studies had low risk of bias. None of the three included studies reported long‐term, patient‐relevant outcomes such as all‐cause mortality, diabetes‐related complications, diabetes‐related mortality, health‐related quality of life, or socioeconomic effects. All three included studies reported that no adverse events were observed, indicating that no deaths occurred (very low‐quality evidence for adverse events, all‐cause mortality, and diabetes‐related mortality). Resveratrol versus placebo showed neutral effects for glycosylated haemoglobin A1c (HbA1c) levels (mean difference (MD) 0.1%, 95% confidence interval (CI) ‐0.02 to 0.2; P = 0.09; 2 studies; 31 participants; very low‐certainty evidence). Due to the short follow‐up period, HbA1c results have to be interpreted cautiously. Similarly, resveratrol versus placebo showed neutral effects for fasting blood glucose levels (MD 2 mg/dL, 95% CI ‐2 to 7; P = 0.29; 2 studies; 31 participants), and resveratrol versus placebo showed neutral effects for insulin resistance (MD ‐0.35, 95% CI ‐0.99 to 0.28; P = 0.27; 2 studies; 36 participants). We found eight ongoing RCTs with approximately 800 participants and two studies awaiting assessment, which, when published, could contribute to the findings of this review.
Authors' conclusions
Currently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM. The limited available research does not provide sufficient evidence to support any effect, beneficial or adverse, of four to five weeks of 10 mg to 1000 mg of resveratrol in adults with T2DM. Adequately powered RCTs reporting patient‐relevant outcomes with long‐term follow‐up periods are needed to further evaluate the efficacy and safety of resveratrol supplementation in the treatment of T2DM.
The fundamental role played by connexins including connexin43 (Cx43) in forming intercellular communication channels (gap junctions), ensuring electrical and metabolic coupling between cells, has ...long been recognized and extensively investigated. There is also increasing recognition that Cx43, and other connexins, have additional roles, such as the ability to regulate cell proliferation, migration, and cytoprotection. Multiple phosphorylation sites, targets of different signaling pathways, are present at the regulatory, C-terminal domain of Cx43, and contribute to constitutive as well as transient phosphorylation Cx43 patterns, responding to ever-changing environmental stimuli and corresponding cellular needs. The present paper will focus on Cx43 in the heart, and provide an overview of the emerging recognition of a relationship between Cx43, its phosphorylation pattern, and development of resistance to injury. We will also review our recent work regarding the role of an enhanced phosphorylation state of Cx43 in cardioprotection. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
► Connexin43 is required to develop protein kinase C-mediated cytoprotection. ► Protective stimuli elicit Cx43 hyper-phosphorylation at specific sites. ► Cardioprotection-linked connexin43 phosphorylation is likely affecting several subcellular domains.
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Implementation strategies are vital for the uptake of evidence to improve health, healthcare delivery, and decision-making. Medical or mental emergencies may be life-threatening, especially in ...children, due to their unique physiological needs when presenting in the emergency departments (EDs). Thus, practice change in EDs attending to children requires evidence-informed considerations regarding the best approaches to implementing research evidence. We aimed to identify and map the characteristics of implementation strategies used in the emergency management of children.
We conducted a scoping review using Arksey and O'Malley's framework. We searched four databases Medline (Ovid), Embase (Ovid), Cochrane Central (Wiley) and CINAHL (Ebsco) from inception to May 2019, for implementation studies in children (≤21 years) in emergency settings. Two pairs of reviewers independently selected studies for inclusion and extracted the data. We performed a descriptive analysis of the included studies.
We included 87 studies from a total of 9,607 retrieved citations. Most of the studies were before and after study design (n = 68, 61%) conducted in North America (n = 63, 70%); less than one-tenth of the included studies (n = 7, 8%) were randomized controlled trials (RCTs). About one-third of the included studies used a single strategy to improve the uptake of research evidence. Dissemination strategies were more commonly utilized (n = 77, 89%) compared to other implementation strategies; process (n = 47, 54%), integration (n = 49, 56%), and capacity building and scale-up strategies (n = 13, 15%). Studies that adopted capacity building and scale-up as part of the strategies were most effective (100%) compared to dissemination (90%), process (88%) and integration (85%).
Studies on implementation strategies in emergency management of children have mostly been non-randomized studies. This review suggests that 'dissemination' is the most common strategy used, and 'capacity building and scale-up' are the most effective strategies. Higher-quality evidence from randomized-controlled trials is needed to accurately assess the effectiveness of implementation strategies in emergency management of children.
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Aims The cardioprotective agent fibroblast growth factor 2 (FGF-2) was found previously to promote phosphorylation of connexin-43 (Cx43) at protein kinase C (PKC) sites such as serine (S) 262 at ...levels above those of non-stimulated hearts. We asked if other PKC-dependent cardioprotective treatments cause a similar effect, and if Cx43 phosphorylation at S262 mediates resistance to injury. Methods and results Isolated perfused adult rat hearts were subjected to the following treatments: ischaemic preconditioning (PC); diazoxide perfusion; FGF-2 pre-treatment followed by 30 min global ischaemia; 30 min global ischaemia followed by 60 min reperfusion in the presence or absence of FGF-2. Cx43 phosphorylation was assessed by western blotting with phospho-specific antibodies. Neonatal cardiomyocyte cultures were used to examine the effect of expressing Cx43 incapable of being phosphorylated at S262 due to an S to alanine (A) substitution on simulated ischaemia-induced cell death (TUNEL staining) and injury (lactic dehydrogenase release). Ischaemic PC, diazoxide, and FGF-2 pre-ischaemic or post-ischaemic treatments elicited a P*Cx43 state, defined as above-physiological levels of phospho-S262-Cx43 and phospho-S368-Cx43. P*Cx43 was sustained during global ischaemia and was accompanied by attenuation of ischaemia-induced Cx43 dephosphorylation and prevention of Cx43 lateralization. Post-ischaemic FGF-2 treatment also diminished dephosphorylated Cx43. Modest overexpression of S262A-Cx43, but not wild-type Cx43, exacerbated cardiomyocyte death and injury caused by simulated ischaemia in vitro. It also prevented the cytoprotective effects of FGF-2 or overexpressed PKCϵ. Conclusions P*Cx43 marks a state of enhanced resistance to ischaemic injury promoted by PKC-activating treatments such as FGF-2 administration or ischaemic PC. Cx43 phosphorylation at S262 likely mediates PKCϵ-dependent cardioprotection.
ObjectivesTo provide a comprehensive systematic overview of current evidence from pooled analyses/meta-analyses and systematic reviews (PMASRs) pertaining to dairy consumption and incident cancer ...and/or all-cause or cancer-specific mortality.DesignOverview of reviews.SettingCommunity setting.ParticipantsThe unit of analysis is PMASRs. A total of 42 PMASRs was included in this overview of reviews.Interventions/exposuresAny dairy product consumption (eg, milk, yogurt, etc).Primary and secondary outcomes measuresPrimary outcome measure is development of any type of cancer. Secondary outcome measures are all-cause mortality and cancer-specific mortality.ResultsFrom 9693 citations identified, we included 42 PMASRs (52 study reports) published between 1991 and 2017. Thirty-one (74%) of these was pooled analyses/meta analyses, and only 11 (26%) were systematic reviews and meta-analyses. There was a wide variability in the type of study designs included within the other PMASRs, thus contributing to variable and, in instances, divergent estimates of cancer risk for several cancer subtypes. For example, only one systematic review and meta-analysis exclusively included prospective study designs. Most PMASRs were of low to moderate quality based on the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scores. The median AMSTAR score was 5 (IQR 2–7). Our overview identified conflicting evidence from PMASRs on association between dairy consumption and incident cancers or mortality. Heterogeneity in summary estimates reflected the inclusion of variable study designs and overall low methodological quality of individual PMASRs.ConclusionsThe association between dairy consumption and cancer risk has been explored in PMASRs with a variety of study designs and of low to moderate quality. To fully characterise valid associations between dairy consumption and risk of cancer and/or mortality rigorously conducted, PMASRs including only high-quality prospective study designs are required.Trial registration numberCRD42017078463.
To assess the real-world interrater reliability (IRR), interconsensus reliability (ICR), and evaluator burden of the Risk of Bias (RoB) in Nonrandomized Studies (NRS) of Interventions (ROBINS-I), and ...the ROB Instrument for NRS of Exposures (ROB-NRSE) tools.
A six-center cross-sectional study with seven reviewers (2 reviewer pairs) assessing the RoB using ROBINS-I (n = 44 NRS) or ROB-NRSE (n = 44 NRS). We used Gwet’s AC1 statistic to calculate the IRR and ICR. To measure the evaluator burden, we assessed the total time taken to apply the tool and reach a consensus.
For ROBINS-I, both IRR and ICR for individual domains ranged from poor to substantial agreement. IRR and ICR on overall RoB were poor. The evaluator burden was 48.45 min (95% CI 45.61 to 51.29).
For ROB-NRSE, the IRR and ICR for the majority of domains were poor, while the rest ranged from fair to perfect agreement. IRR and ICR on overall RoB were slight and poor, respectively. The evaluator burden was 36.98 min (95% CI 34.80 to 39.16).
We found both tools to have low reliability, although ROBINS-I was slightly higher. Measures to increase agreement between raters (e.g., detailed training, supportive guidance material) may improve reliability and decrease evaluator burden.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Asthma management guidelines recommend low‐dose inhaled corticosteroids (ICS) as first‐line therapy for adults and adolescents with persistent asthma. The addition of anti‐leukotriene ...agents to ICS offers a therapeutic option in cases of suboptimal control with daily ICS.
Objectives
To assess the efficacy and safety of anti‐leukotriene agents added to ICS compared with the same dose, an increased dose or a tapering dose of ICS (in both arms) for adults and adolescents 12 years of age and older with persistent asthma. Also, to determine whether any characteristics of participants or treatments might affect the magnitude of response.
Search methods
We identified relevant studies from the Cochrane Airways Group Specialised Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the Allied and Complementary Medicine Database (AMED), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the trial registries clinicaltrials.gov and ICTRP from inception to August 2016.
Selection criteria
We searched for randomised controlled trials (RCTs) of adults and adolescents 12 years of age and older on a maintenance dose of ICS for whom investigators added anti‐leukotrienes to the ICS and compared treatment with the same dose, an increased dose or a tapering dose of ICS for at least four weeks.
Data collection and analysis
We used standard methods expected by Cochrane. The primary outcome was the number of participants with exacerbations requiring oral corticosteroids (except when both groups tapered the dose of ICS, in which case the primary outcome was the % reduction in ICS dose from baseline with maintained asthma control). Secondary outcomes included markers of exacerbation, lung function, asthma control, quality of life, withdrawals and adverse events.
Main results
We included in the review 37 studies representing 6128 adult and adolescent participants (most with mild to moderate asthma). Investigators in these studies used three leukotriene receptor antagonists (LTRAs): montelukast (n = 24), zafirlukast (n = 11) and pranlukast (n = 2); studies lasted from four weeks to five years.
Anti‐leukotrienes and ICS versus same dose of ICS
Of 16 eligible studies, 10 studies, representing 2364 adults and adolescents, contributed data. Anti‐leukotriene agents given as adjunct therapy to ICS reduced by half the number of participants with exacerbations requiring oral corticosteroids (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.29 to 0.86; 815 participants; four studies; moderate quality); this is equivalent to a number needed to treat for additional beneficial outcome (NNTB) over six to 16 weeks of 22 (95% CI 16 to 75). Only one trial including 368 participants reported mortality and serious adverse events, but events were too infrequent for researchers to draw a conclusion. Four trials reported all adverse events, and the pooled result suggested little difference between groups (RR 1.06, 95% CI 0.92 to 1.22; 1024 participants; three studies; moderate quality). Investigators noted between‐group differences favouring the addition of anti‐leukotrienes for morning peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), asthma symptoms and night‐time awakenings, but not for reduction in β2‐agonist use or evening PEFR.
Anti‐leukotrienes and ICS versus higher dose of ICS
Of 15 eligible studies, eight studies, representing 2008 adults and adolescents, contributed data. Results showed no statistically significant difference in the number of participants with exacerbations requiring oral corticosteroids (RR 0.90, 95% CI 0.58 to 1.39; 1779 participants; four studies; moderate quality) nor in all adverse events between groups (RR 0.96, 95% CI 0.89 to 1.03; 1899 participants; six studies; low quality). Three trials reported no deaths among 834 participants. Results showed no statistically significant differences in lung function tests including morning PEFR and FEV1 nor in asthma control measures including use of rescue β2‐agonists or asthma symptom scores.
Anti‐leukotrienes and ICS versus tapering dose of ICS
Seven studies, representing 1150 adults and adolescents, evaluated the combination of anti‐leukotrienes and tapering‐dose of ICS compared with tapering‐dose of ICS alone and contributed data. Investigators observed no statistically significant difference in % change from baseline ICS dose (mean difference (MD) ‐3.05, 95% CI ‐8.13 to 2.03; 930 participants; four studies; moderate quality), number of participants with exacerbations requiring oral corticosteroids (RR 0.46, 95% CI 0.20 to 1.04; 542 participants; five studies; low quality) or all adverse events (RR 0.95, 95% CI 0.83 to 1.08; 1100 participants; six studies; moderate quality). Serious adverse events occurred more frequently among those taking anti‐leukotrienes plus tapering ICS than in those taking tapering doses of ICS alone (RR 2.44, 95% CI 1.52 to 3.92; 621 participants; two studies; moderate quality), but deaths were too infrequent for researchers to draw any conclusions about mortality. Data showed no improvement in lung function nor in asthma control measures.
Authors' conclusions
For adolescents and adults with persistent asthma, with suboptimal asthma control with daily use of ICS, the addition of anti‐leukotrienes is beneficial for reducing moderate and severe asthma exacerbations and for improving lung function and asthma control compared with the same dose of ICS. We cannot be certain that the addition of anti‐leukotrienes is superior, inferior or equivalent to a higher dose of ICS. Scarce available evidence does not support anti‐leukotrienes as an ICS sparing agent, and use of LTRAs was not associated with increased risk of withdrawals or adverse effects, with the exception of an increase in serious adverse events when the ICS dose was tapered. Information was insufficient for assessment of mortality.
A new tool, "risk of bias (ROB) instrument for non-randomized studies of exposures (ROB-NRSE)," was recently developed. It is important to establish consistency in its application and interpretation ...across review teams. In addition, it is important to understand if specialized training and guidance will improve the reliability in the results of the assessments. Therefore, the objective of this cross-sectional study is to establish the inter-rater reliability (IRR), inter-consensus reliability (ICR), and concurrent validity of the new ROB-NRSE tool. Furthermore, as this is a relatively new tool, it is important to understand the barriers to using this tool (e.g., time to conduct assessments and reach consensus-evaluator burden).
Reviewers from four participating centers will apprise the ROB of a sample of NRSE publications using ROB-NRSE tool in two stages. For IRR and ICR, two pairs of reviewers will assess the ROB for each NRSE publication. In the first stage, reviewers will assess the ROB without any formal guidance. In the second stage, reviewers will be provided customized training and guidance. At each stage, each pair of reviewers will resolve conflicts and arrive at a consensus. To calculate the IRR and ICR, we will use Gwet's AC
statistic. For concurrent validity, reviewers will appraise a sample of NRSE publications using both the Newcastle-Ottawa Scale (NOS) and ROB-NRSE tool. We will analyze the concordance between the two tools for similar domains and for the overall judgments using Kendall's tau coefficient. To measure evaluator burden, we will assess the time taken to apply ROB-NRSE tool (without and with guidance), and the NOS. To assess the impact of customized training and guidance on the evaluator burden, we will use the generalized linear models. We will use Microsoft Excel and SAS 9.4, to manage and analyze study data, respectively.
The quality of evidence from systematic reviews that include NRSE depends partly on the study-level ROB assessments. The findings of this study will contribute to an improved understanding of ROB-NRSE and how best to use it.
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