Desensitizing Toothpastes for Dentin Hypersensitivity: A Network Meta-analysis.

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.

Colorectal cancer guidelines seldom include the patient perspective.

OBJECTIVES: This study aimed to describe how colorectal practice guidelines (PGs) incorporate the patient perspective. STUDY DESIGN AND SETTING: We searched in the Guidelines International Network library, MEDLINE, National Guideline Clearinghouse, NHS Evidence database, and TRIP database. Two authors independently selected the PGs. We considered recommendations rated or worded as weak or conditional or suggesting multiple options, as potentially preference sensitive. Two authors independently evaluated if, in potentially sensitive recommendations, the patient perspective was incorporated. RESULTS: We included 28 PGs that contained 588 recommendations, being 256 potentially preference sensitive. Ten PGs (36%) included patients in the development process, and 12 (43%) provided information about patients' perspectives. Nine PGs (32%) included recommendations in which the patient perspective was explicitly considered, and 13 (46.4%) that recommended a discussion with the patient. From a total of 588 recommendations, 9.7% (25/256) of potentially preference-sensitive recommendations considered the patient perspective. The inclusion of patients in the development process was associated with a more frequent incorporation of the patient perspective in potentially preference sensitive recommendations (70% vs. 0%; P < 0.001). CONCLUSIONS: Guideline users should be aware that the incorporation of the patient perspective in colorectal cancer PGs is suboptimal. Guideline developers should make efforts to incorporate the patient perspective, especially in preference-sensitive recommendations.

2020 ARIA CARE PATHWAYS FOR ALLERGIC RHINITIS - GEORGIA.

Allergic rhinitis is the most common chronic disease worldwide. Treatment guidelines have improved the knowledge on rhinitis and have had a significant impact on AR management. In 20 years, ARIA has considerably evolved from the first multi-morbidity guideline in respiratory diseases to the digital transformation of health and care. Allergic rhinitis in Georgia, Next-generation ARIA-GRADE guidelines and ARIA, 2020 care pathways for Allergen Immunotherapy have been discussed in this review.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome.

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Vitamin D supplementation in primary allergy prevention: Systematic review of randomized and non-randomized studies.

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.

Prebiotics for the prevention of allergies: A systematic review and meta-analysis of randomized controlled trials.

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.

NHF-McMaster Guideline on Care Models for Haemophilia Management.

This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia.

Methodology for the development of the NHF-McMaster Guideline on Care Models for Haemophilia Management.

BACKGROUND: Rigorous and transparent methods are necessary to develop clinically relevant and evidence-based practice guidelines. We describe the development of the National Hemophilia Foundation-McMaster Guideline on Care Models for Haemophilia Management, which addresses best practices in haemophilia care delivery. METHODS: We assembled a Panel of persons with haemophilia (PWH), parents of PWH, clinical experts and guideline methodologists. Conflicts of interest were disclosed and managed throughout. Panel members and key stakeholders were surveyed to develop the guideline questions and identify patient-important outcomes. Systematic reviews of the literature were conducted for all factors important in decision-making: benefits and harms; patient values and preferences; resource implications; acceptability; equity; and feasibility. We used the GRADE approach to create evidence profiles to evaluate the evidence and present key results. Evidence to Decision frameworks were created to guide the Panel in making evidence-based recommendations. When evidence was very low quality or not available, evidence from other chronic disease populations was presented to the Panel to inform the recommendations. Additionally, we systematically pooled observations from experts, and conducted qualitative interviews exploring key stakeholder experiences and perspectives. The Panel made recommendations for each guideline question and elaborated on research priorities, implementation considerations, and monitoring. Final recommendations were circulated for public and peer review. CONCLUSIONS: Despite the paucity of high-quality evidence typical of a rare condition such as haemophilia, we successfully applied a rigorous and transparent methodology based on GRADE to develop an evidence-based clinical practice guideline.

Integrated multidisciplinary care for the management of chronic conditions in adults: an overview of reviews and an example of using indirect evidence to inform clinical practice recommendations in the field of rare diseases.

BACKGROUND: Integrated care models have been adopted for individuals with chronic conditions and for persons with rare diseases, such as haemophilia. OBJECTIVE: To summarize the evidence from reviews for the effects of integrated multidisciplinary care for chronic conditions in adults and to provide an example of using this evidence to make recommendations for haemophilia care. SEARCH METHODS: We searched MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews up to January 2016, and reviewed reference lists of retrieved papers. SELECTION CRITERIA: Systematic reviews of at least one randomized study, on adults with non-communicable chronic conditions. DATA COLLECTION AND ANALYSIS: Two investigators independently assessed eligibility and extracted data. Quality of reviews was assessed using ROBIS, and the evidence assessed using GRADE. RESULTS: We included seven reviews reporting on three chronic conditions. We found low to high quality evidence. Integrated care results in a reduction in mortality; likely a reduction in emergency visits and an improvement in function; little to no difference in quality of life, but shorter hospital stays; and may result in little to no difference in missed days of school or work. No studies reported educational attainment, or patient adherence and knowledge. When used for haemophilia, judgment about the indirectness of the evidence was driven by disease, intervention or outcome characteristics. CONCLUSION: This overview provides the most up to date evidence on integrated multidisciplinary care for chronic conditions in adults, and an example of how it can be used for guidelines in rare diseases.

Care models in the management of haemophilia: a systematic review.

BACKGROUND: Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes. OBJECTIVE: To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH). SEARCH METHODS: We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists. SELECTION CRITERIA: Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery. DATA COLLECTION AND ANALYSIS: Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate. RESULTS: 27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking. CONCLUSION: Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed.

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

A guide to GRADE guidelines for the readers of JTH.

More than 70 organizations worldwide have adopted the GRADE methodology for guideline development. The ninth iteration of the American Collage of Chest Physicians guidelines (AT9) adopted structural and policy changes that resulted in a greater adherence to GRADE guidance than previous iterations. The most important of these changes include minimizing the impact of financial and intellectual conflict of interest, increasing the rigor of evidence evaluation, acknowledging uncertainty in estimates of typical values and preferences, and awareness of the large variability in values and preferences. One of the consequences of the greater adherence to GRADE methodology is an increase in weak vs. strong recommendations in AT9. The result of the GRADE process highlights the desirability of higher-quality evidence both regarding the outcomes of alternative management strategies and regarding the distribution of values and preferences in patients considering those alternatives. It also encourages shared decision making in encounters between physicians and patients. Although some physicians might find the uncertainty underlying medical practice discouraging or unsettling, relative to denying or obscuring the uncertainty, acknowledging and addressing the uncertainty will lead to more credible, realistic, and useful recommendations.

Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

[ARIA (Allergic Rhinitis and its Impact on Asthma) achievements in 10 years and future needs]. / ARIA (allerjik rinit ve astim üzerine etkisi) 10 yildaki kazanimlar ve gelecekteki gereksinimler.

Allergic rhinitis and asthma represent global health problems for all age groups. Asthma and rhinitis frequently co-exist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization (WHO) workshop in 1999 and was published in 2001. ARIA has reclassified allergic rhinitis as mild/moderate-severe and intermittent/persistent. This classification schema closely reflects the impact of allergic rhinitis on patients. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of allergic rhinitis and asthma co-morbidities based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation). ARIA has been disseminated and implemented in over 50 countries of the world. In Turkey, it is important to make a record of ARIA achievements and to identify the still unmet clinical, research and implementation needs in order to strengthen the 2011 EU Priority on allergy and asthma in children.

Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis.

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.