The impact of outdoor pollution and extreme temperatures on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO2, SO2, O3, and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence).

The impact of indoor pollution on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new-onset asthma (incidence) and (ii) adverse asthma-related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new-onset asthma and critical and important asthma-related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new-onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new-onset asthma and with asthma severity (low level of certainty). Exposure to pesticides and VOCs may increase the risk of new-onset asthma (very low certainty evidence). The impact on asthma-related outcomes of all major indoor pollutants is uncertain. As the level of certainty is low or very low for most of the available evidence on the impact of indoor pollutants on asthma-related outcomes more rigorous research in the field is warranted.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Is exposure to pollen a risk factor for moderate and severe asthma exacerbations?

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.

Treatment with anticancer drugs for advanced pancreatic cancer: a systematic review.

BACKGROUND: Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes. METHODS: We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach. RESULTS: We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status. CONCLUSIONS: The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.

Systemic oncological treatments in patients with advanced pancreatic cancer: a scoping review and evidence map.

PURPOSE: To identify, describe, and organise currently available evidence regarding systemic oncological treatments (SOTs) (chemotherapy, targeted/biological therapies, and immunotherapy) compared to best supportive care (BSC) for patients with advanced pancreatic cancer (PC). METHODS: We conducted a scoping review and evidence mapping, adhering to PRISMA-ScR checklist. We searched MEDLINE, EMBASE, Cochrane Library, Epistemonikos, PROSPERO, and clinicaltrials.gov for eligible studies. We included systematic reviews (SRs), randomised controlled trials (RCTs), quasi-experimental, and observational studies evaluating SOTs compared to BSC or no treatment in patients with advanced PC. Two independent reviewers performed the screening process and data extraction. We developed evidence maps as an interactive visualization display, including the assessed interventions and outcomes. RESULTS: Of the 50,601 records obtained from our search, we included 43 studies: 2 SRs, 16 RCTs, 4 quasi-experimental studies, 20 observational studies, and 1 protocol for a quasi-experimental study. Forty-two studies reported survival-related outcomes and most favoured SOTs, while five reported toxicity and most favoured BSC. Other patient-centred outcomes, such as quality of life, were scarcely reported. CONCLUSIONS: This study highlights the current evidence gaps in studies assessing treatments for patients with advanced PC, mainly the lack of reports of non-survival-related outcomes, pointing out research areas that need further attention to make better recommendations for these patients.

Effect of oral health interventions for dependent older people-A systematic review.

BACKGROUND: There is an increasing proportion of older people in the population worldwide, with a large group being dependent on the care of others. Dependent older people are more vulnerable to oral diseases, which can heavily impact their quality of life (OHRQoL) and general health. OBJECTIVE: The purpose of this systematic review was to comprehensively assess interventions to improve oral health or guarantee access and adherence to dental treatment of dependent older people. METHODS: We searched MEDLINE, EMBASE, CENTRAL and clinical trial registries. Two reviewers performed the selection, data extraction, risk of bias evaluation using the Cochrane Risk of Bias tool and assessment of certainty of the evidence. When possible, we conducted a meta-analysis to calculate effect estimates and their 95%CIs. Primary outcomes were OHRQoL, oral/dental health, and use of the oral care system. RESULTS: We included a total of 30 randomised clinical trials assessing educational and non-educational interventions for community-dwelling older people (n = 2) and those residing in long-term care facilities (n = 28). Most studies assessed oral hygiene and showed that interventions may result in a reduction in dental plaque in the short term (with low certainty of evidence), but there is limited evidence for long-term effectiveness. Only one study assessed OHRQoL, and none evaluated changes in the use of the oral health care system. CONCLUSION: Our findings do not provide strong conclusions in favour of any specific intervention, mainly due to study quality and imprecision. There is limited information about the long-term effect of interventions, and further research is needed, especially targeting community-dwelling older people. PROSPERO ID: CRD42021231721.

Systemic Oncological Treatments versus Supportive Care for Patients with Advanced Hepatobiliary Cancers: An Overview of Systematic Reviews.

BACKGROUND: The trade-off between systemic oncological treatments (SOTs) and UPSC in patients with primary advanced hepatobiliary cancers (HBCs) is not clear in terms of patient-centred outcomes beyond survival. This overview aims to assess the effectiveness of SOTs (chemotherapy, immunotherapy and targeted/biological therapies) versus UPSC in advanced HBCs. METHODS: We searched for systematic reviews (SRs) in PubMed, EMBASE, the Cochrane Library, Epistemonikos and PROSPERO. Two authors assessed eligibility independently and performed data extraction. We estimated the quality of SRs and the overlap of primary studies, performed de novo meta-analyses and assessed the certainty of evidence for each outcome. RESULTS: We included 18 SRs, most of which were of low quality and highly overlapped. For advanced hepatocellular carcinoma, SOTs showed better overall survival (HR = 0.62, 95% CI 0.55-0.77, high certainty for first-line therapy; HR = 0.85, 95% CI 0.79-0.92, moderate certainty for second-line therapy) with higher toxicity (RR = 1.18, 95% CI 0.87-1.60, very low certainty for first-line therapy; RR = 1.58, 95% CI 1.28-1.96, low certainty for second-line therapy). Survival was also better for SOTs in advanced gallbladder cancer. No outcomes beyond survival and toxicity could be meta-analysed. CONCLUSION: SOTs in advanced HBCs tend to improve survival at the expense of greater toxicity. Future research should inform other patient-important outcomes to guide clinical decision making.

Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map.

Introduction: Despite being commonly recommended, the impact of anticancer drugs (ACDs) on patient-important outcomes beyond survival for advanced hepatobiliary cancers (HBCs) may not have been sufficiently assessed. We aim to identify and map the evidence regarding ACDs versus best supportive care (BSC) for advanced HBCs, considering patient-centered outcomes. Methods: In this mapping review, we included systematic reviews, randomized controlled trials, quasi-experimental, and observational studies comparing ACDs (chemotherapy, immunotherapy, biological/targeted therapy) versus BSC for advanced HBCs. We searched MEDLINE (PubMed), EMBASE (Ovid), Cochrane Library, Epistemonikos, PROSPERO and clinicaltrials.gov for eligible studies. Two reviewers performed the screening and data extraction processes. We developed evidence maps for each type of cancer. Results: We included 87 studies (60 for advanced liver cancer and 27 for gallbladder or bile duct cancers). Most of the evidence favored ACDs for survival outcomes, and BSC for toxicity. We identified several evidence gaps for non-survival outcomes, including quality of life or quality of end-of-life care. Discussion: Patient-important outcomes beyond survival in advanced HBCs are insufficiently assessed by the available evidence. Future studies need to address these gaps to better inform decision-making processes.

Direct materials for restoring caries lesions: Systematic review and meta-analysis-a report of the American Dental Association Council on Scientific Affairs.

BACKGROUND: The goal of restoring caries lesions is to protect the pulp, prevent progression of the disease process, and restore the form and function of the tooth. The purpose of this systematic review was to determine the effect of different direct restorative materials for treating cavitated caries lesions on anterior and posterior primary and permanent teeth. TYPE OF STUDIES REVIEWED: The authors included parallel and split-mouth randomized controlled trials comparing the effectiveness of direct restorative materials commercially available in the United States placed in vital, nonendodontically treated primary and permanent teeth. Pairs of reviewers independently conducted study selection, data extraction, and assessments of risk of bias and certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The authors conducted pair-wise meta-analyses to summarize the evidence and calculated measures of association and their 95% CIs. RESULTS: Thirty-eight randomized controlled trials were eligible for analysis, which included data on Class I and Class II restorations on primary teeth and Class I, Class II, Class III, Class V, and root surface restorations on permanent teeth. Included studies assessed the effect of amalgam, resin composite, compomer, conventional glass ionomer cement, resin-modified glass isomer cement, and preformed metal crowns. Moderate to very low certainty evidence suggested varying levels of effectiveness across restorative materials. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Owing to a relatively low event rate across various outcomes indicating restoration failure, there was limited evidence to support important differences between direct restorative materials used in practice.

Oral Health-Related Quality of Life Changes in Patients with Dentofacial Deformities Class II and III after Orthognathic Surgery: A Systematic Review and Meta-Analysis.

Our aim was to assess the impact of combined orthodontic-surgical treatment on patients' oral health-related quality of life (OHRQoL) according to type of dentofacial deformities, by synthesizing the available evidence. METHODS: Search was conducted in the PubMed, Embase/MEDLINE, Scopus, and Cochrane databases. The eligibility criteria were studies that measured OHRQoL before-after orthognathic surgery, with results disaggregated by Class II and III. Two researchers independently performed the selection process, data extraction, and methodological quality assessment. Meta-analysis of the standard mean differences (SMD) was performed using random effect models. RESULTS: The search identified 1047 references. Thirteen studies met the inclusion criteria, and four were included in the meta-analysis. The SMD of OHRQL global score showed large improvement 4-7 months after surgery in Class II and III patients (2.09, 95% CI 0.68 to 3.49 and 1.96, 95% CI 1.22 to 2.70, respectively). The sensitivity analyses, excluding studies with weak methodological quality, showed that Class III patients' improvement in functional limitation was significantly higher than in Class II patients (SMD 0.57, 95% CI 0.12-1.02). CONCLUSIONS: There is not enough evidence to support differences between Class II and III patients in the OHRQoL impact after orthognathic surgery, but findings suggest lower improvement of some domains in Class II patients.

Effectiveness of pre-surgical orthopedics on patients with cleft lip and palate: A systematic review and meta-analysis.

OBJECTIVE: Evaluate the effectiveness of pre-surgical orthopedics (PSO) in patients with cleft lip palate (CLP) in maxillary morphology (MM), facial growth and development (FGD), occlusal alterations (OA), parental satisfaction (PS), and side effects. DESIGN: Systematic review and meta-analysis of randomized and controlled clinical trials. Searches was performed in CENTRAL, MEDLINE, and EMBASE. RESULTS: From the eight studies included, three are randomized clinical trials, and five clinical trials are controlled. MM was evaluated by the intercanine width (Mean difference (MD) =1.44; CI95%= -0.30, 3.19; very low certainty), anteroposterior length (MD=1.32; CI95%= -0.59, 3.24; very low certainty) and intertuberocity width (MD=0.09; CI95%= -0.68, 0.49; certainty: very low). FGD was evaluated by SNA angle (MD: 1.29; P = 0.306; moderate certainty), SNB angle (MD: -0.79; P = 0.550; moderate certainty) and ANB angle (MD: 1; P = 0.362; moderate certainty). OA was evaluated by 5-years-old-index (MD= -0.09; P = 0.49; moderate certainty) and by Huddart score (MD=0.51; P = 0.736; moderate certainty). A valid questionnaire assessed PS only in one study (MD= -0.1; P = 0.199; moderate certainty). No studies reported side effects. CONCLUSION: Due to the uncertainty of the effect of PSO on MM and the lack of clinically relevant effect on FGD, OA, or PS, it is not reasonable to include this intervention as a treatment until future studies clarify its effect.

Effectiveness and Safety of Dabigatran Compared to Vitamin K Antagonists in Non-Asian Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Real-life data about the use of dabigatran in patients with non-valvular atrial fibrillation are warranted. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of dabigatran, globally and stratified by dose (110/150 mg twice daily), vs vitamin K antagonists in non-Asian patients with non-valvular atrial fibrillation from "real-world" studies. METHODS: A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement) statement. The ROBINS-I tool was used to assess bias risk. MEDLINE and EMBASE, from inception up to May 2021, using appropriate controlled vocabulary and free search terms, were searched.  RESULTS: A total of 34 studies, corresponding to 37 articles involving 1,600,722 participants (1,154,283 exposed to vitamin K antagonists and 446,439 to dabigatran) were eligible for this review. Dabigatran 150 mg reduced the risk of ischemic stroke compared with vitamin K antagonists, with a 14% risk reduction (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.74-0.98). Globally, dabigatran reduced the risk of all-cause mortality compared with vitamin K antagonists (HR 0.76, 95% CI 0.69-0.84), with a greater effect observed with dabigatran 150 mg (HR 0.65, 95% CI 0.58-0.73). There was a trend towards a lower risk of myocardial infarction with dabigatran 150 mg (HR 0.86, 95% CI 0.71-1.04). Regarding the primary safety outcomes, dabigatran (either at a dose of 150 mg or 110 mg) reduced the risk of major bleeding compared with vitamin K antagonists (HR 0.77, 95% CI 0.70-0.83), as well as the risk of intracranial bleeding (HR 0.44, 95% CI 0.39-0.50) and fatal bleeding (HR 0.76, 95% CI 0.60-0.95), but with a slight increase in gastrointestinal bleeding risk (HR 1.16, 95% CI 1.08-1.26). CONCLUSIONS: Dabigatran has a favorable impact on effectiveness and safety outcomes compared with vitamin K antagonists in real-world populations.

Efficacy of systemic oncological treatments in patients with advanced pancreatic cancer at high risk of dying in the short or medium-term: overview of systematic reviews.

BACKGROUND: Patients with advanced pancreatic cancer (PC) have a high risk of dying in the short or medium-term. This overview aimed to assess the evidence regarding systemic oncological treatments (SOT) versus supportive care for advanced PC. METHODS: We searched for systematic reviews (SRs) in MEDLINE, Embase, The Cochrane Library, Epistemonikos, and PROSPERO. Two authors assessed eligibility independently. Data extraction and methodological quality assessment were conducted by one author and cross-checked by another one. We evaluated the overlap of primary studies, performed a de novo meta-analysis, and assessed the certainty of evidence. Primary outcomes were overall survival (OS), quality of life (QoL), functional status (FS), and toxicity. RESULTS: We identified three SRs that assessed SOT versus supportive care in patients with advanced PC. All SRs had critically low methodological quality. At 12 months, OS improved with chemotherapy, radiotherapy followed by chemotherapy, and immunotherapy, but the certainty of the evidence supporting these findings is very low. The evidence on chemotherapy is very uncertain about its effects on QoL; it suggests a slight increase in toxicity and little to no difference in FS. The evidence on immunotherapy is very uncertain about its effects in toxicity. CONCLUSIONS: The identified evidence is very uncertain about the benefits of oncological treatments on OS and QoL in patients with advanced PC with a high risk of dying in the short or medium-term, so its use should be proposed only to selected patients. Further studies that include a thorough assessment of patient-centred outcomes are needed.

Risk of bias in dentistry-related randomized controlled trials in spanish language journals

Objectives: To assess the risk of bias (RoB) of randomized controlled trials (RCTs) published in dental journals in the Spanish language. Methods: A systematic retrospective survey was conducted of all RCTs published from 1980 to 2019 in dentistry Spanish and Latin American journals. We extracted data and performed RoB assessments using the Cochrane Risk of Bias tool. Results: 292 RCTs published in 51 journals were included. The best-rated domains were incomplete outcome data, selective reporting, and other biases. The domains assessed with higher proportions of an unclear or high risk of bias were sequence generation, allocation concealment, and blinding of outcome assessment. There is a low proportion of RCTs published in Spanish language journals. However, the number has been increasing over the years, and the low risk of bias assessment rates across domains show an increasing trend. Conclusions: A low percentage of Spanish-language dental journals issue RCTs. Our assessment of these RCTs' RoB suggests higher difficulties in the design and conduction phase than in the posterior reporting stage.

Riesgo de hemorragia postquirúrgica en pacientes bajo tratamiento antitrombótico sometidos a cirugía oral: Revisión Sistemática y Metaanálisis / Risk of postsurgical hemorrhage in patients with antitrombotic treatment undergoing oral surgery: A systematic review and Metanalysis

RESUMEN: Introducción: el objetivo de esta revisión fue determinar el riesgo de hemorragia postoperatoria en pacientes con tratamiento anticoagulante oral (TACO) sometidos a cirugía oral que no suspenden su tratamiento comparado con quienes lo modifican o suspenden. Materiales y métodos: se realizó una búsqueda en CENTRAL, Medline y EMBASE, junto con una revisión manual de revistas especializadas y resúmenes de la IADR. Dos revisores realizaron la selección de estudios, evaluación de riesgo de sesgo y extracción de datos de forma independiente. Se seleccionaron los ensayos clínicos aleatorizados que miden la aparición de hemorragias en pacientes sometidos a procedimientos quirúrgicos orales con TACO en comparación con un grupo que interrumpió o modificó su terapia. Resultados: Solo 5 estudios cumplieron los criterios de inclusión (549 pacientes). El metanálisis mostró que el mantenimiento de la TACO no aumenta el riesgo de hemorragia postoperatoria (riesgo relativo: 1,41 [0,93 - 2,16], IC del 95% p = 0,11) en comparación con la interrupción del tratamiento. Conclusión: Aunque se encontró una mayor cantidad de hemorragia postoperatoria en pacientes con TACO comparado con quienes lo interrumpieron o modificaron, esta diferencia no fue estadística ni clínicamente significativa. Por lo tanto, TACO no debe suspenderse en pacientes sometidos a cirugía oral.

ABSTRACT: Introduction: This systematic review aims to determine the postoperative bleeding risk in patients on oral anticoagulant therapy (OAT) undergoing oral surgical procedures when continuing with the treatment, compared with those modifying or discontinuing the treatment. Materials and methods: A search was performed using CENTRAL, Medline and EMBASE, in conjunction with a manual review of indexes of specialized journals and abstracts of the IADR. Study selection, assessments of risk of bias and data extraction were performed independently by 2 reviewers. Randomized clinical trials measuring the occurrence of bleeding in patients on OAT undergoing oral surgical procedures compared with a group discontinuing or modifying their therapy were selected. Results: A total of 5 studies were included based on inclusion criteria (549 patients). The meta-analysis showed that the maintenance of OAT does not increases the risk of postoperative bleeding (relative risk [RR] 1.41 [0.93 - 2.16]; 95% CI p= 0,11) compared with the discontinuation of therapy. Conclusion: Although a larger quantity of oral postoperative bleeding episodes were found in patients continuing with OAT compared with patients discontinuing or modifying their therapy, this difference was neither statistically nor clinically significant. Therefore, OAT should not be discontinued in patients undergoing oral surgery.