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Background: Inhaled corticosteroids (ICS) are commonly prescribed medications for the management of asthma and chronic obstructive pulmonary disease. It is well established that long-term use of these drugs may lower bone mineral density. However, whether ICS increase the risk of fractures remains unknown. Recent studies that have attempted to explore this risk have had conflicting results. We sought to explore the risk of ICS and fractures among older adults by conducting a systematic review and meta-analysis of the literature.Methods: We systematically searched several databases, including MEDLINE, EMBASE and the Cochrane Library, to identify pertinent studies. Those studies that potentially met our inclusion criteria were identified by two reviewers. Relative risks (RRs) were pooled using the random effects model. We also explored dose-response by stratifying the analysis on high and low doses of ICS. Heterogeneity was assessed using the Q statistic and publication bias was assessed using the funnel plot.Results: Thirteen studies, including four randomized controlled trials, were included in the review. The pooled RRs for hip fractures and any fractures were 0.91 (95% CI 0.87, 0.96) and 1.02 (95% CI 0.96, 1.08), respectively. When we restricted the analysis to users of high-dose ICS, the pooled RRs for any fractures and hip fractures were 1.30 (95% CI 1.07, 1.58) and 1.32 (95% CI 0.90, 1.92), respectively. The funnel plot did not show evidence of publication bias.Conclusion: We found no association between the use of ICS and fractures in older adults. A slight increase in risk was seen in those using high-dose ICS. The significance of this association should be investigated further. [ABSTRACT FROM AUTHOR]

Objective To estimate worldwide iodine nutrition and monitor country progress towards sustained elimination of iodine deficiency disorders. Methods Cross-sectional data on urinary iodine (UI) and total goitre prevalence (TGP) in school-age children from 1993-2003 compiled in the WHO Global Database on Iodine Deficiency were analysed. The median UI was used to classify countries according to the public health significance of their iodine nutrition status. Estimates of the global and regional populations with insufficient iodine intake were based on the proportion of each country's population with UI below 100 [mu]g/l. TGP was computed for trend analysis over 10 years. Findings UI data were available for 92.1% of the world's school-age children. Iodine deficiency is still a public health problem in 54 countries. A total of 36.5% (285 million) school-age children were estimated to have an insufficient iodine intake, ranging from 10.1% in the WHO Region of the Americas to 59.9% in the European Region. Extrapolating this prevalence to the general population generated an estimate of nearly two billion individuals with insufficient iodine intake. Iodine intake was more than adequate, or excessive, in 29 countries. Global TGP in the general population was 15.8%. Conclusion Forty-three countries have reached optimal iodine nutrition. Strengthened UI monitoring is required to ensure that salt iodization is having the desired impact, to identify at-risk populations and to ensure sustainable prevention and control of iodine deficiency. Efforts to eliminate iodine deficiency should be maintained and expanded. [ABSTRACT FROM AUTHOR]

Background: Recently, studies have attempted to explore the interaction between ACE inhibitors and aspirin (acetylsalicylic acid) when both drugs are used concomitantly to reduce mortality in patients with coronary artery disease. Results have been conflicting due, in part, to sub-optimal methods used to explore this interaction.Methods: We reviewed systematically all studies on mortality in patients treated with ACE inhibitors and aspirin and conducted a meta-analysis in order to explore the interaction between both drugs and resolve discrepancies. To be included, each study had to provide data on mortality of patients who received both drugs, either drug and no drug. These data were necessary to calculate the synergy index (S) and its 95% confidence interval (CI) that we used to quantify the effect due to interaction between ACE inhibitors and aspirin. After testing for heterogeneity of effects, we pooled the S values from the individual studies into one summary measure. Subsequently, we compared our results with those obtained through the most common but incorrect method of evaluating interaction. This method uses significance testing of the relative risk of mortality when a 'product term' between ACE inhibitors and aspirin is entered in a logistic regression model.Results: Eight studies met the inclusion criteria. The pooled synergy index S indicates slight but precise antagonism between ACE inhibitors and aspirin (S = 0.91; 95% CI 0.80 to 1.03). In contrast, the pooled 'product term' is not significant and would have lead to the conclusion of absence of interaction (p = 0.15).Conclusion: There seems to be an antagonistic interaction between ACE inhibitors and aspirin. Former discrepancies were due to inadequate assessment of interaction. Results from the Studies on Left Ventricular Dysfunction (SOLVD) and Heart Outcome Prevention Evaluation (HOPE) trials that assessed the effect of combined administration of ACE inhibitors and aspirin were not included in this meta-analysis because those trials did not provide enough data to compute the S statistic. It is possible that results from on-going trials such as Women's Atovarstatin Trial on Cholesterol (WATCH) will shed more light on ACE inhibitor and aspirin interaction in the future. [ABSTRACT FROM AUTHOR]

At the time a new drug is placed on the market, information on its therapeutic effect and toxicity is limited. Because of its simplicity and widespread use, the voluntary reporting by clinical physicians is the main method for detecting rare or unexpected adverse drug events (ADEs). However, the usefulness of this method may be compromised if the reporting rate is low. We present the results of a questionnaire-based case-control study carried out among 692 physicians from Galicia (north-west region of Spain), in which we assessed their attitudes and opinions towards ADEs. In general, the Galician physicians think it is difficult to link a given ADE with a drug (P < 0.05) and have very heterogeneous opinions on the fact that very severe ADEs are known before the drug is commercialized. They globally disagree with the proposal that ADE reporting should be renumerated and the fact that ADE reporting can be risky for the physician. Some of the beliefs concerning ADEs are incorrect. It is crucial to improve the training of the physicians through active educational strategies based on personal contact. [ABSTRACT FROM AUTHOR]

Background: Recent case reports and letters have alerted practitioners to the risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson's disease treated with pramipexole and ropinirole.Objective: To quantify the risk of somnolence with the new dopamine agonists pramipexole and ropinirole in patients with Parkinson's disease.Methods: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articles to include. Information on randomisation, blinding, type of treatment and reporting of somnolence were abstracted by 2 independent reviewers. Disagreements were resolved by a third author.Analysis: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnolence with these drugs (plus levodopa) versus that with levodopa alone. We calculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model.Results: Four trials were included in the analysis of patients taking pramipexole or ropinirole compared with those taking placebo. The pooled relative risk of somnolence in this analysis was 4.98 [95% confidence interval (CI) 1.79 to 13.89]. Seven trials were included in the analysis of patients taking levodopa and pramipexole or ropinirole compared with those taking levodopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88).Conclusion: Patients with Parkinson's disease using pramipexole or ropinirole are at higher risk of experiencing somnolence relative to patients taking placebo. Patients taking levodopa plus either one of these dopamine agonists are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescribing these drugs. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the factors associated with the decision to dispense a drug and those related with the decision to recommend the customer to visit a doctor. The authors carried out a cohort study on a sample of 166 pharmacists in northwest Spain. They gathered 7010 patient counseling interventions. During a personal interview, they collected information on the pharmacist's education and specialty, and on the characteristics of the pharmacy, and its socioeconomic environment. Greater experience of the pharmacist, being a pharmacy owner, and a more advanced age of the patient were associated with a lower level of prescription. In contrast, being a female patient and working in a pharmacy that has a heavy workload were associated with a higher level of prescription.

The relation between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and severity of COVID-19 has been the subject to debate since the outbreak of the pandemic. Despite speculations about the possible harmful or protective effects, the position currently most supported by the scientific community is that there is no association between use of NSAIDs and COVID-19 outcomes. With the aim of contributing to increase the body of evidence on this issue, we conducted a case-control study using real-world data to investigate the association between prior use of NSAIDs, by active ingredient and type (traditional NSAIDs and selective COX-2 inhibitors), and important COVID-19-related outcomes, including susceptibility, PCR + patient progression, and hospitalisation. Our findings suggest that, in general, the use of traditional NSAIDs is not associated with any adverse COVID-19 outcome. However, we observed a possible association between diclofenac and a higher risk of PCR + patient progression. Our results also suggest that selective COX-2 inhibitors might be related with a reduction in the risk of PCR + patient progression. These results suggest that, with the possible exception of diclofenac, the use of NSAIDs should not be advised against for relief of symptoms in patients with COVID-19. In addition, they support the importance of continue to investigate the treatment potential of selective COX-2 inhibitors in the management of COVID-19, something that could have significant implications for the treatment of this disease and other viral infections., (© 2024. The Author(s).)

Introduction: The relation between physical well-being and chronic pain is complex and involves several subjective and objective covariates. We aimed to assess the role of mediator, confounder, or interactor played by covariates, including sleep quality, physical activity, perceived stress, smoking, and alcohol drinking in the relation between physical well-being and chronic pain. Method: We used Poisson regression to obtain incidence rate ratios (IRR) of the association between physical well-being and chronic pain in a cohort study carried out among university students. We applied General Structural Equation Modeling (GSEM) to assess mediation and stratum-specific analyses to distinguish confounding from interaction. We computed Relative Excess Risks due to Interaction (RERI), Attributable Proportion (AP), and the Synergy index (S) to measure additive interaction. Results: High physical well-being is related to a large decrease in the risk of chronic pain (IRR Total Effect = 0.58; 95% CI: 0.50-0.81). Perceived stress mediates 12.5% of the total effect of physical well-being on chronic pain. The stratum-specific IRRs of current smokers and non-current smokers were different from each other and were larger than the crude IRR (IRR = 1.49; 95% CI: 1.24-1.80), which indicates that smoking could be both confounder and interactor. Interaction analyses showed that physical activity could act as a potential interactor (RERI = 0.25; 95% CI: 0.13, 0.60). Conclusions: Perceived stress is an important mediator of the relation between physical well-being and chronic pain, while smoking is both a confounder and an interactor. Our findings may prove useful in distinguishing high-risk groups from low-risk groups, in the interventions aimed at reducing chronic pain.

Background: Chronic pain and depression represent two global health problems with considerable economic consequences. Although existing literature reports on the relation between depression and pain conditions, meta-analytic evidence backing the mediating role of sleep disturbance as one of the main symptoms of depression is scarce. To examine the extent to which sleep disturbance mediates the depression-chronic pain association, we conducted a systematic review and meta-analysis of the associations of chronic pain, depression, and sleep quality., Methods: We systematically searched for literature in MEDLINE and other relevant databases and identified cohort and case-control studies on depression, sleep disturbance, and chronic pain. Forty-nine studies were eligible, with a total population of 120 489 individuals. We obtained direct and indirect path coefficients via two-stage meta-analytic structural equation modelling, examined heterogeneity via subgroup analyses, and evaluated primary studies quality., Results: We found a significant, partial mediation effect of sleep disturbance on the relation between depression and chronic pain. The pooled path coefficient (coef.) of the indirect effect was 0.03 (95% confidence interval [CI]: 0.01-0.05) and accounted for 12.5% of the total effect of depression on chronic pain. This indirect effect also existed for cohort studies (coef. 0.02; 95% CI: 0.002-0.04), European studies (coef. 0.03; 95% CI: 0.004-0.05), and studies that adjusted for confounders (coef. 0.04; 95% CI: 0.01-0.09)., Conclusions: Sleep disturbance partially mediates the association between depression and pain. Although plausible mechanisms could explain this mediation effect, other explanations, including reverse causation, must be further explored., Systematic Review Protocol: PROSPERO CRD42022338201., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To undertake a meta-analysis of the association of Oral Lichen Planus (OLP) with diabetes, two diseases with an important impact on public health and the economy, but the evidence of which about their association is inconsistent., Methods: Relevant studies were localized by searching MEDLINE, EMBASE, Conference Proceedings, and other databases from inception to October 2020, without restrictions. The reference lists of included studies and of related reviews were also inspected. Global pooled odds ratios were calculated, and predefined subgroup analyses were performed. The heterogeneity between studies and publication bias was assessed and sensitivity analysis was carried out., Results: Thirty-two studies were included in the meta-analysis. Pooled ORs showed a moderate association between diabetes and OLP [OR: 1.87 (95%CI: 1.57, 2.34)]. The association is limited to studies carried out on adults only [OR: 2.12 (95%CI: 1.75, 2.57)] and is observed in all study designs. Globally, the heterogeneity was low to moderate. Studies carried out in European populations show a stronger association of diabetes and OLP than Asiatic studies [OR: 2.49 (95%CI: 1.87, 3.32) and 1.60 (95%CI: 1.25, 2.03), respectively]., Conclusions: Diabetes and OLP are moderately associated. Systematic diagnosis of diabetes in OLP patients could prove useful., (This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.© 2021 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Objective: Recurrent aphthous stomatitis (RAS) is a condition that affects 20% of the world population and is characterized by painful ulcers in the oral mucosa. So far, the epidemiology and risk factors of RAS have been infrequently studied. Our objective was to determine whether sleep-related factors are related to the occurrence of RAS in the first prospective study carried out on this topic., Methods: A cohort of 11210 Spanish students, 13-17 years old, was followed up for one year. Sleep disorders were assessed at baseline using a standard validated questionnaire., Results: We detected 2655 new cases of RAS with a total of 287,262 person-week of follow-up. Subjects with high (4th quartile) Insomnia Index showed an incidence rate ratio (IRR) of RAS of 1.29 (95% confidence interval (CI) 1.15-1.45), while subjects with high Hypersomnia Index presented an IRR of 1.42 (95% CI 1.26-1.61). A high score of sleep-related phenomena was also associated with an increased IRR: 1.53 (95% CI 1.37-1.69). Adolescents with high level of sleep satisfaction were at lower risk of RAS: 0.88 (95% CI 0.77-1.01)., Conclusion: These findings suggest that sleep disorders are moderately associated with RAS in adolescents., (wileyonlinelibrary.com/journal/odi.)

Introduction: Chronic pain represents a global health problem with a considerable economic burden. The relation of alcohol intake and chronic pain conditions was assessed in several studies with conflicting results. We used dose-response meta-analysis techniques to answer the question of whether alcohol intake is related to chronic pain occurrence., Methods: We searched MEDLINE, Embase, and other databases to identify cohort and case-control studies on alcohol consumption and chronic pain. Sixteen studies were eligible with a total population of 642 587 individuals. Fixed-effects and random-effects pooled estimates were obtained by weighting log odds ratios (ORs) in case-control studies and log incidence rate ratios in cohort studies by the inverse of their variance. A heterogeneity assessment and a dose-response analysis were carried out. Quality scoring was also performed., Results: Our results show that any alcohol consumption was related to lower odds of chronic pain (pooled OR=0.76; 95% confidence interval [CI], 0.61-0.95). The association was non-linear. The ORs by quartile of alcohol doses were as follows: OR 2nd quartile =0.74; 95% CI, 0.64-0.87; OR 3rd quartile =0.67; 95% CI, 0.53-0.86; and OR 4th quartile=0.75; 95% CI, 0.50-1.14. This association was observed for cohort studies (OR=0.77; 95% CI, 0.61-0.98) and European studies (OR=0.65; 95% CI, 0.48-0.87) only. Studies with complete adjustment for confounding factors showed a stronger relation than those with incomplete adjustment (OR=0.69; 95% CI, 0.48-0.99 and OR=0.85; 95% CI, 0.65-1.11, respectively)., Conclusion: Alcohol consumption presents a non-linear inverse association with the occurrence of chronic pain. Although plausible mechanisms could explain this protective effect, other explanations, including reverse causation, are probable., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: To quantify the association between income and antibiotic misuse including unprescribed use, storage of antibiotics and non-adherence., Methods: We identified pertinent studies through database search, and manual examination of reference lists of selected articles and review reports. We performed a dose-response meta-analysis of income, both continuous and categorical, in relation to antibiotic misuse. Summary odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated under a random-effects random effects model., Results: Fifty-seven studies from 22 countries of different economic class were included. Overall, the data are in agreement with a flat linear association between income standardized to socio-economic indicators and antibiotic misuse (OR per 1 unit increment = 1.00, p-value = 0.954, p-value non-linearity = 0.429). Data were compatible with no association between medium and high income with general antibiotic misuse (OR 1.04; 95% CI 0.89, 1.20 and OR 1.03; 95% CI 0.82, 1.29). Medium income was associated with 19% higher odds of antibiotic storage (OR 1.19; 95% CI 1.07, 1.32) and 18% higher odds of any aspect of antibiotic misuse in African studies (OR 1.18; 95% CI 1.00, 1.39). High income was associated with 51% lower odds of non-adherence to antibiotic treatment (OR 0.49; 95% CI 0.34, 0.60). High income was also associated with 11% higher odds of any antibiotic misuse in upper-middle wealth countries (OR 1.11; 95% CI 1.00, 1.22)., Conclusions: The association between income and antibiotic misuse varies by type of misuse and country wellness. Understanding the socioeconomic properties of antibiotic misuse should prove useful in developing related intervention programs and health policies., (© 2021. The Author(s).)

Objective: To measure the association between knowledge, attitudes and practices of personal misuse of tranquilizers among parents of schoolchildren in Beirut (Lebanon)., Design: We carried out a cross-sectional study in 1396 adults recruited from parents of students of eleven public and private schools, from primary schools to high schools, using a Knowledge, Attitude and Practices (KAP) questionnaire of personal use of tranquilizers., Main Outcome Measures: We assessed five patterns of tranquilizers' misuse: unprescribed use, shortened treatment, stored leftovers, doubled forgotten doses or taken when remembered, changed dose without medical recommendation, and a sixth composite outcome: 'any misuse'., Results: Sixty-three (62.2%) of 91 parents who used tranquilizers reported at least one misuse pattern. Higher odds of 'any misuse' were observed among parents who reported taking tranquilizers to sleep better, to enjoy themselves with their families or to work better [2.35 ≤ adjusted interquartile odds ratio (aIqOR) ≤ 1.99]. Storing tranquilizers for future need was strongly associated with misuse [aIqOR: 5.00 (95% CI: 3.30, 7.59)]. Greater awareness about hazards of tranquilizers and the importance of therapeutic compliance was associated with lower odds of specific misuse patterns (0.50 ≤ aIqOR ≤ 0.72)., Conclusions: Poor knowledge and medically disapproved attitudes increase the likelihood of practices of tranquilizer misuse.

Objectives: To assess the relationship between social factors (socio-economic status, household load and job strain) and chronic pain occurrence, and the role of gender in this relationship., Methods: We used data corresponding to 8 years of follow-up of the Stockholm Public Health Cohort Study (2006-2014) to compute Adjusted Incidence Rate Ratios (IRRs) and additive interaction measures of chronic pain episodes, social factors, and sex in 16 687 subjects., Results: For men, increased rates of chronic pain occurrence were observed for skilled workers (IRR = 1.27, 95% CI: 0.99, 1.61) and lower non-manual employees (IRR = 1.37, 95% CI: 1.05, 1.78), compared with unskilled workers; subjects with high household load (IRR = 1.39; 95% CI: 1.03, 1.88), compared with those with a null score; and subjects with active jobs (IRR = 1.27, 95% CI: 1.06, 1.51), compared with those with low-strain jobs. For women, we observed decreased rates of chronic pain occurrence in lower (IRR = 0.82, 95% CI: 0.68, 0.99), intermediate (IRR = 0.74, 95% CI: 0.63, 0.88) and higher non-manual employees (IRR = 0.65, 95% CI: 0.54, 0.79), compared with unskilled workers. Compared with subjects with a null score, women with low household load showed a lower rate of chronic pain occurrence (IRR = 0.85; 95% CI: 0.72, 1.00). Compared with subjects with low-strain jobs, those with passive jobs (IRR = 1.21; 95% CI: 1.02, 1.44) and high-strain jobs (IRR = 1.46; 95% CI: 1.02, 2.09) showed higher rates of chronic pain occurrence., Conclusion: In general, our analysis yielded different, if not opposite, results when data were stratified by sex. Sex may then represent an effect modifier of the relationship between social factors and chronic pain., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Numerous studies evaluated the association of education level with misuse of antibiotics by the general population, yet divergent findings were reported. Therefore, a meta-analysis was conducted to summarize this association., Methods: A categorical and continuous dose-response meta-analysis of the association of education level with antibiotic misuse was undertaken. Summary odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using random-effect model., Results: The meta-analysis included 85 studies from 42 countries of different socioeconomic status. Compared to low education (≤ 9 years), medium education (> 9-12 years) is associated with 20% lower odds of antibiotic misuse in high-income countries (OR = 0.80; 95% CI 0.66, 0.97), while high education (> 12 years) is associated with 14% lower odds of any aspect of antibiotic misuse (OR = 0.86; 95% CI 0.72, 1.03). The association is more pronounced in Middle East (OR = 0.64; 95% CI 0.42, 1.00) and countries of lower-middle economies (OR = 0.67, 95% CI 0.41, 1.11). Inversely, in Europe, high education is associated with 25% higher odds of antibiotic misuse (OR = 1.25, 95% CI 1.00, 1.58). Each additional year of education was associated with 4% lower odds of any aspect of antibiotic misuse in lower-middle economies (OR = 0.96; 95% CI 0.92, 1.00) and in Middle East (OR = 0.96; 95% CI 0.93, 1.00). Conversely, it was associated with 3% higher odds of antibiotic storage, a specific type of misuse (OR = 1.03, 95% CI 1.01, 1.06)., Conclusion: Individuals misuse antibiotics irrespective of their education level. Intervention programs to enhance the proper use of antibiotics should target all communities independent of their education level., (© 2022. The Author(s).)

Objectives: Validated knowledge-attitude-practice (KAP) questionnaires are essential to design and evaluate intervention programs on antibiotic use. Recently, we validated the first KAP questionnaire on antibiotics in Spain. Cross-cultural adaptation and validation of research tools increase their universal usefulness. Here, we aimed to validate the questionnaire in a developing country with different socioeconomic characteristics from that of Spain., Methods: We translated the previously developed KAP-questionnaire into Arabic and French, tailored it and then validated it in adult population in Lebanon. The item content validity index (I-CVI), scale content validity index (S-CVI/Ave) and modified Kappa (k*) were calculated. The construct validity of the questionnaire was evaluated using confirmatory factorial analysis (CFA, N = 1460) and its reliability was assessed using intraclass correlation coefficients (ICC, N = 100) and Cronbach's alpha statistic., Results: ICV-I (>0.78), k* (equal to ICV-I for all items) and S-CVI/Ave (≥0.95) confirmed the questionnaire content validity. Pilot testing (N = 40) and face validity showed the understandability of the questionnaire by the population. Test-retest reliability analysis (N = 100) yielded ICC ≥ 0.59 for all knowledge and attitude items, showing the capacity of the questionnaire to generate reproducible results. CFA evidenced adequate fit of the chosen model, thus establishing the construct validity of the questionnaire (root mean squared error approximation = 0.053, standardized root mean square residual = 0.045, comparative fit index = 0.92 and Tucker-Lewis index = 0.90). The questionnaire showed an acceptable internal reliability (Cronbach's alpha = 0.62) and was highly accepted in Lebanon (response rate = 96% and item response rates ≥ 94%)., Conclusions: The validity of the KAP-questionnaire on antibiotics in Arabic and French was demonstrated in Lebanon.

Background: Gastroesophageal reflux disease (GORD) is highly prevalent and often coexists with asthma exacerbation. Divergent findings about the association between the two diseases were reported. We conducted a systematic review and meta-analysis to determine whether there exists an association between GORD and asthma., Methods: We searched MEDLINE, EMBASE, and other databases and then performed a manual search, to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using fixed- and random-effect models. We evaluated the quality of included studies, explored heterogeneity between studies, undertook subgroup analyses, assessed publication bias, and performed sensitivity analyses., Results: We identified 32 eligible studies, conducted in 14 countries and including a total of 1,612,361 patients of all ages. Overall, GORD shows a weak association with asthma exacerbation (OR = 1.27; 95% CI 1.18-1.35). This association was observed in cohort, case-control, and cross-sectional designs and in European as well as non-European populations. Subgroup analyses show that GORD is associated with frequent asthma exacerbations (≥3 exacerbations, OR = 1.59; 95% CI 1.13-2.24) and with exacerbations needing oral corticosteroid therapy (OR = 1.24; 95% CI 1.09-1.41). GORD pediatric patients are at higher odds of asthma exacerbation than adults. We did not detect any evidence of publication bias and the association between GORD and asthma exacerbation held in all undertaken sensitivity analyses., Conclusions: Gastroesophageal reflux disease and asthma exacerbation are weakly associated., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objectives: To identify the immunohistochemical pattern of non-tumoral epithelium adjacent to lip cancer (ANTE) to unveil molecular alterations and potential biomarkers in lip cancer patients., Materials and Methods: A systematic search at MEDLINE, EMBASE and proceedings Web of Science, OpenGrey and WorldCat. The PICOS outline (Population: lip cancer patients; Intervention: immunostaining with biomarkers in surgical specimens; Comparisons: ANTE versus LC; Outcomes: primary-to identify the immunohistochemical pattern of peritumoral epithelium and secondary-to assess the immunoreactivity of LC epithelium; and Study design: cross-sectional, case-control and cohort studies)., Results: A total of 339 records were identified. Seven studies reporting on ANTE and LCs were included in the qualitative synthesis, and 4 of them (p53 immunostaining) were selected for meta-analysis. In the ANTE group, the pooled prevalence of p53 was 0.74 (95% CI: 0.66 - 0.82), while in the lip squamous cell carcinoma group this prevalence was 0.83 (95% CI: 0.75 - 0.89)., Conclusions: Similar immunoexpression was found in lip epithelium adjacent to lip carcinoma, even in epithelia with normal appearance or mild histological alterations. The role of biomarkers in the follow-up of actinic cheilitis patients deserves additional clinical assessment., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)