Summary
Cow's milk is a common cause of food allergy in children. Children usually outgrow cow's milk allergy by the age of 3–5 years, but some will have persistent symptoms beyond childhood. We ...performed a systematic review of randomized controlled trials (RCTs) and observational studies to assess the evidence supporting the use of oral immunotherapy in IgE‐mediated cow's milk allergy to inform the World Allergy Organization guidelines. Of 1034 screened articles published until May 2011, five RCTs and five observational studies fulfilled a priori specified inclusion criteria. RCTs including 218 patients showed that oral immunotherapy, compared to elimination diet alone, increased the likelihood of achieving full tolerance of cow's milk relative risk: 10.0 (95% CI: 4.1–24.2). Adverse effects of immunotherapy include frequent local symptoms (16% of doses), mild laryngospasm relative risk: 12.9 (1.7–98.6), mild asthma rate ratio: 3.8 (2.9–5.0), reactions requiring oral glucocorticosteroids relative risk: 11.3 (2.7–46.5) or intramuscular epinephrine injection rate ratio 5.8 (1.6–21.9). Results of observational studies were consistent with those of RCTs. Despite the availability of RCTs, the overall low quality of evidence leaves important uncertainty about anticipated effects of immunotherapy due to very serious imprecision of the estimates of effects and the likelihood of publication bias for some of the critical outcomes. A potentially large benefit of oral immunotherapy in patients with cow's milk allergy may be counterbalanced by frequent and sometimes serious adverse effects. Additional, larger RCTs measuring all patient‐important outcomes are still needed.
Numerous randomised controlled trials (RCTs) published in first tier medical journals have evaluated the health effects of diets high in protein. We conducted a rigorous systematic review of RCTs ...comparing higher- and lower-protein diets.
We searched several electronic databases up to July 2011 for studies focusing on patient-important outcomes (for example, cardiovascular disease) and secondary outcomes such as risk factors for chronic disease (for example, adiposity).
We identified 111 articles reporting on 74 trials. Pooled effect sizes using standardised mean differences (SMDs) were small to moderate and favoured higher-protein diets for weight loss (SMD -0.36, 95% confidence interval (CI) -0.56 to -0.17), body mass index (-0.37, CI -0.56 to 0.19), waist circumference (-0.43, CI -0.69 to -0.16), blood pressure (systolic: -0.21, CI -0.32 to -0.09 and diastolic: -0.18, CI -0.29 to -0.06), high-density lipoproteins (HDL 0.25, CI 0.07 to 0.44), fasting insulin (-0.20, CI -0.39 to -0.01) and triglycerides (-0.51, CI -0.78 to -0.24). Sensitivity analysis of studies with lower risk of bias abolished the effect on HDL and fasting insulin, and reduced the effect on triglycerides. We observed nonsignificant effects on total cholesterol, low-density lipoproteins, C-reactive protein, HbA1c, fasting blood glucose, and surrogates for bone and kidney health. Adverse gastrointestinal events were more common with high-protein diets. Multivariable meta-regression analysis showed no significant dose response with higher protein intake.
Higher-protein diets probably improve adiposity, blood pressure and triglyceride levels, but these effects are small and need to be weighed against the potential for harms.
Background
To date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken.
Objective
To review the efficacy and ...safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies.
Methods
Three databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Results
Among the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children.
Conclusion
Limited information is available addressing primary prevention of allergic diseases after vitamin D supplementation, and its potential impact remains uncertain.
The goal of this systematic review and network meta-analysis was to compare the relative effects of toothpaste formulations for dentin hypersensitivity (DH), tested in randomized controlled trials ...(RCTs). We searched 7 databases to February 2019. Paired reviewers independently screened studies, extracted data, and performed risk of bias assessment. The outcome of interest was painful response measured through tactile, cold, and air stimuli. We conducted a random-effects Bayesian network meta-analysis using standardized mean difference (SMD) and their credible intervals (CIs) as the measure of effect for each pain stimuli. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included 125 RCTs (12,541 patients). For tactile stimulus, the following active ingredients showed large beneficial effects compared to fluoride with moderate certainty of evidence (SMD; 95% CI): potassium + stannous fluoride (SnF2) (3.05; 1.69–4.41), calcium sodium phosphosilicate (CSP) (2.14; 0.75–3.53), SnF2 (2.02; 1.06–2.99), potassium + hydroxyapatite (2.47; 0.3–4.64), strontium (1.43; 0.46–2.41), and potassium (1.23; 0.48–1.98). For cold stimulus, CSP showed large beneficial effects compared to fluoride (3.93; 0.34–7.53) with moderate certainty; for air stimulus, arginine (2.22; 1.45–2.99), potassium + hydroxyapatite (2.44; 0.33–4.55), potassium + SnF2 (2.28; 0.87–3.69), CSP (1.98; 0.99–2.98), and SnF2 (1.9; 1.03–2.77) showed large beneficial effects compared to fluoride with moderate to high certainty. Most toothpaste formulations showed evidence of superiority against placebo or fluorides (amine fluoride, sodium monofluorophosphate, or sodium fluoride). CSP was most beneficial for all 3 stimuli with high to moderate certainty. SnF2 alone and potassium combined with SnF2 or hydroxyapatite were beneficial for tactile and air stimulus with high to moderate certainty. Arginine was beneficial for air stimulus, and strontium and potassium were beneficial for tactile stimulus, with moderate certainty.
Network meta-analysis (NMA), combining direct and indirect comparisons, is increasingly being used to examine the comparative effectiveness of medical interventions. Minimal guidance exists on how to ...rate the quality of evidence supporting treatment effect estimates obtained from NMA. We present a four-step approach to rate the quality of evidence in each of the direct, indirect, and NMA estimates based on methods developed by the GRADE working group. Using an example of a published NMA, we show that the quality of evidence supporting NMA estimates varies from high to very low across comparisons, and that quality ratings given to a whole network are uninformative and likely to mislead.
There is uncertainty about the interpretation of changes in the 6-min walk distance (6MWD) in chronic obstructive pulmonary disease (COPD) patients and whether the minimal important difference (MID) ...for this useful outcome measure exists. Data were used from nine trials enrolling a wide spectrum of COPD patients with 6MWD at baseline and follow-up and used to determine threshold values for important changes in 6MWD using three distribution-based methods. Anchor-based methods to determine a MID were also evaluated. Data were included of 460 COPD patients with a mean+/-sd forced expiratory volume in one second (FEV(1)) of 39.2+/-14.1% predicted and 6MWD of 361+/-112 m at baseline. Threshold values for important effects in 6MWD were between 29 and 42 m, respectively, using the empirical rule effect size and the standardised response mean. The threshold value was 35 m (95% confidence interval 30-42 m) based on the standard error of measurement. Correlations of 6MWD with patient-reported anchors were too low to provide meaningful MID estimates. 6-min walk distance should change by approximately 35 m for patients with moderate to severe chronic obstructive pulmonary disease in order to represent an important effect. This corresponds to a 10% change of baseline 6-min walk distance. The low correlations of 6-min walk distance with patient-reported anchors question whether a minimal important difference exists for the 6-min walk distance.
Summary
Background
Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first‐degree relative. Prebiotics are selectively fermented food ...ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies.
Objective
To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines.
Methods
We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies.
Results
Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: −0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results.
Conclusions
Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain.
The GRADE approach to grading the quality of evidence and strength of recommendations provides a comprehensive and transparent approach for developing clinical recommendations about using diagnostic ...tests or diagnostic strategies. Although grading the quality of evidence and strength of recommendations about using tests shares the logic of grading recommendations for treatment, it presents unique challenges. Guideline panels and clinicians should be alert to these special challenges when using the evidence about the accuracy of tests as the basis for clinical decisions. In the GRADE system, valid diagnostic accuracy studies can provide high quality evidence of test accuracy. However, such studies often provide only low quality evidence for the development of recommendations about diagnostic testing, as test accuracy is a surrogate for patient-important outcomes at best. Inferring from data on accuracy that using a test improves outcomes that are important to patients requires availability of an effective treatment, improved patients' wellbeing through prognostic information, or - by excluding an ominous diagnosis - reduction of anxiety and the opportunity for earlier search for an alternative diagnosis for which beneficial treatment can be available. Assessing the directness of evidence supporting the use of a diagnostic test requires judgments about the relationship between test results and patient-important consequences. Well-designed and conducted studies of allergy tests in parallel with efforts to evaluate allergy treatments critically will encourage improved guideline development for allergic diseases.
The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance to grading the quality of underlying evidence and the strength of recommendations in health ...care. The GRADE system's conceptual underpinnings allow for a detailed stepwise process that defines what role the quality of the available evidence plays in the development of health care recommendations. The merit of GRADE is not that it eliminates judgments or disagreements about evidence and recommendations, but rather that it makes them transparent. This first article in a three-part series describes the GRADE framework in relation to grading the quality of evidence about interventions based on examples from the field of allergy and asthma. In the GRADE system, the quality of evidence reflects the extent to which a guideline panel's confidence in an estimate of the effect is adequate to support a particular recommendation. The system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, consistency and precision of the results, and directness of the evidence.
To cite this article: Brożek JL, Akl EA, Compalati E, Kreis J, Terracciano L, Fiocchi A, Ueffing E, Andrews J, Alonso‐Coello P, Meerpohl JJ, Lang DM, Jaeschke R, Williams JW Jr, Phillips B, Lethaby ...A, Bossuyt P, Glasziou P, Helfand M, Watine J, Afilalo M, Welch V, Montedori A, Abraha I, Horvath AR, Bousquet J, Guyatt GH, Schünemann HJ, for the GRADE Working Group. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 3 of 3. The GRADE approach to developing recommendations. Allergy 2011; 66: 588–595.
This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients’ values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients’ values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.
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