Search

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.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.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: ORAlcohol 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.

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 media-tor, 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 associa-tion between physical well-being and chronic pain in a cohort study carried out among uni-versity students. We applied General Structural Equation Modeling (GSEM) to assess me-diation, and stratum-specific analysis to distinguish confounding from interaction. We computed Relative Excess Risks due to Interaction (RERI), Attributable Proportion (AP), and Synergy index (S) to measure additive interaction. Results: High physical well-being is related to a large decrease in the risk of chronic pain (IRRTotal 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). Conclusion: 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 from low-risk groups, in the interven-tions aimed at reducing chronic pain.

Background Pain, specifically chronic pain, is a major public health issue worldwide with considerable health-related consequences and large economic impact. The relation between socioeconomic status and pain occurrence is well established. However, little is known on the relation between socioeconomic factors and worsening of pain, including progression from non-chronic pain to chronic pain. Methods To assess the relation between socioeconomic status and pain worsening, we used the Stockholm Public Health Cohort Study from 2006 to 2014 and analysed data of 9721 participants who completed follow-up. The adjusted incidence rate ratios (IRRs) of moderate and severe pain worsening episodes were computed, using a pain amplification model, which encompasses spreading, somatisation, and psychological distress components. Multiple imputation analysis was performed subsequently to adjust for cohort attrition. Results Compared with non-skilled workers, self-employed subjects (IRR=1.18; 95% confidence interval [CI], 1.01–1.39) and non-manual employees were at higher risk of moderate worsening (lower non-manual employees: IRR=1.21; 95% CI, 1.03–1.41; intermediate non-manual employees: IRR=1.26; 95% CI, 1.10–1.44; higher non-manual employees: IRR=1.25; 95% CI, 1.08–1.45). This risk increase was limited to worsening starting at stage 0 (non-chronic pain). No association was found between socioeconomic status and severe pain worsening. Conclusion Our results support a moderate association between intermediate and high socioeconomic status, and moderate pain worsening. This association could be explained by the heterogeneous composition of the socioeconomic variable used in this cohort, and by changes in exposure and other time-varying covariables' status during follow-up.

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.

To measure the association between knowledge, attitudes and practices of personal misuse of tranquilizers among parents of schoolchildren in Beirut (Lebanon).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.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'.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).Poor knowledge and medically disapproved attitudes increase the likelihood of practices of tranquilizer misuse.

Objective To examine the association between socioeconomic status (SES) and the occurrence of chronic pain, defined as pain that persists or recurs for >3 months. Methods We performed a structured search in Medline, Embase, WHO Global Index Medicus and Conference Proceedings Citation Index-Science databases to identify cohort and case–control studies on chronic pain and SES and its subgroups (SES combined index, educational level, income and occupational status). We extracted study characteristics, outcome measures and measures of association and their 95% CIs. Literature search, data extraction and risk of bias assessment were conducted by two independent researchers. We performed main and subgroup meta-analyses using random-effects model, and formally assessed heterogeneity and publication bias. Results A total of 45 studies, covering a population of ∼175 000 individuals, were meta-analysed, yielding a pooled Odds Ratio (OR) of 1.32 (95% CI: 1.21, 1.44) and 1.16 (95% CI: 1.09, 1.23) for low and medium SES levels, respectively, compared with high level. We obtained similar results in all the subgroup analyses. Heterogeneity was generally moderate to high across strata, and some evidence of publication bias for low socioeconomic status was found. Conclusion Our results support a moderate increase in the risk of chronic pain for low and medium SES when compared with high SES, a feature that remained constant in all measures of exposure or outcome used. Further prospective research on populations from developing countries are needed to confirm our findings as the studies available for this meta-analysis were carried out exclusively in developed countries.

Background Several studies have investigated the intermediate variables or mediators through which attachment insecurity influence the development of depression. However, there has not been a systematic synthesis of this literature to date. The current meta-analytic review aimed at identifying such mediators and quantifying their effect size. Methods We systematically searched Medline, Pubmed, Psycinfo, Embase, Proceedings Web of Science and ProQuest Dissertations & Theses Global up until May 2019. 108 studies met inclusion criteria (i.e., investigated intermediate variables that explain the effect of attachment insecurity [exposure] on depressive symptoms [outcome]). Standardized regression coefficients of the indirect and total paths of mediation models of 80 studies were pooled using the inverse of their variance as a weight. Studies were coded and ranked for quality. Results Dysfunctional attitudes (β = 0.10, 95% CI = 0.01 to 0.20), self-criticism (β = 0.17, 95% CI = 0.04 to 0.28), low self-compassion (β = 0.16, 95% CI = 0.02 to 0.29), and cognitive hyperactivating regulation strategies (β = 0.13, 95% CI = 0.05 to 0.20), such as repetitive thinking (β = 0.17, 95% CI = 0.07 to 0.28), and particularly, brooding rumination β = 0.20, 95% CI = 0.07 to 0.32), mediated the association between insecure attachment and depressive symptoms. Indirect effects were only significant among adult populations. Limitations The methodological quality of studies was mostly moderate to low and analyses revealed considerable heterogeneity. Conclusion Our findings support the direct targeting of cognitive-emotional psychological mechanisms in prevention programs and treatment of depression. More longitudinal studies are needed to clarify the interplay of such mediators along with other interpersonal factors between insecure attachment and depression.

Background Evidence about the association of high blood eosinophil count with asthma exacerbation is inconsistent and unclear. The objective of this meta-analysis was to determine whether elevated blood eosinophil count predicts asthma exacerbation. Methods We searched MEDLINE, EMBASE, and additional databases, without any language restriction. We also checked the reference lists of the included studies and of relevant systematic reviews. The main outcome was the occurrence of asthma exacerbation. We calculated global pooled odds ratios (ORs) and their 95% confidence intervals (CIs) and performed predefined subgroup analyses. We appraised the quality of the studies using Newcastle-Ottawa Scale, examined the heterogeneity between studies, assessed publication bias, and carried out sensitivity analyses. Results Among 1567 retrieved publications, 23 observational studies comprising 155,772 participants met the inclusion criteria. High blood eosinophil count was associated with higher odds of asthma exacerbation [OR: 1.31 (95% CI: 1.16, 1.49)], specifically with asthma-related outpatient visits [OR: 1.46 (95% CI: 1.25, 1.70)] and emergency department visits [OR: 1.63 (95% CI: 1.29, 2.07)]. A significant association was observed starting from an eosinophils' cutoff value of 200 cells/μl. The association was observed for cohort studies [OR: 1.30 (95%CI: 1.13, 1.49)], North American studies [OR: 1.43 (95%CI: 1.31, 1.57)], Asian populations [OR: 1.67 (95%CI: 1.34, 2.08)], children [OR: 1.38 (95%CI: 1.22, 1.56)], and studies that adjusted for inhaled corticosteroids therapy [OR: 1.42 (95%CI: 1.28, 1.56)]. Conclusions Blood eosinophil counts ≥ 200 cells/µL are associated with asthma exacerbation. Blood eosinophil count is a modifiable factor that could be addressed in asthma management strategies.

Numerous questionnaires are available on Knowledge, Attitudes, and Practices (KAP) towards antibiotics' use by adults, but none of these questionnaires is fully validated. We undertook an exhaustive literature review to design a comprehensive KAP questionnaire concerning the personal use of antibiotics in Galicia, North Spain. The Item Content Validity Index (I-CVI) and modified Kappa statistic (K*), confirmed the content validity of the questions (0.78 ≤ I-CVI ≤ 1.00 and 0.78 ≤ K* ≤ 1.00). The S-CVI statistic showed the content validity of the scale (S-CVI/Ave: 0.95). Following face validity and pilot testing, the Test–Retest Reliability in a sample of 145 adults confirmed the reliability of the questions. We carried out Confirmatory Factor Analysis using cross loadings and modification indices to choose the most adequate model in data collected from 844 adults. We estimated the indicators of model fit and demonstrated that the selected model has a good to excellent fit, thus establishing the construct validity. The final version of the questionnaire was highly accepted by the general adult population as reflected by the response rate (95.85%) and the low percentage of unanswered questions (0.4–2.7%). Our fully validated questionnaire could prove useful for research as it permits generating high quality data and reducing measurement error.

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.

Tranquilizer misuse is an emerging international public health concern. The psychosocial determinants of this misuse remain understudied. Instruments to measure the Knowledge, Attitudes and Practices (KAP) of tranquilizer misuse are unavailable, except for a recently published questionnaire validated in the Spanish language. We translated the KAP questionnaire into Arabic and French, adapted it and undertook a complete validation procedure in the general adult population in Lebanon. The content validity indicators were good: item content validity index ranged between 0.89 and 1.00, the content validity index scale average was ≥0.95 and the modified Kappa statistic for each of the KAP items was equal to I-CVI. The intra-class correlation coefficient values (n = 100) were ≥0.62 for all Knowledge and Attitudes items, demonstrating the item reliability. Confirmatory factorial analysis (n = 1450) showed that the selected model of Knowledge and Attitude constructs has adequate fit indicators and encompassed three factors that showed acceptable internal reliability: Knowledge (Cronbach’s alpha = 0.72), personal Attitudes towards tranquilizers (Cronbach’s alpha = 0.79) and Attitudes towards healthcare providers (Cronbach’s alpha = 0.65). The Arabic/French questionnaire was highly accepted, with a response rate of 95.72% and item non-response rate ≤3.6%. The availability of a cross-cultural adapted and multilingual validated questionnaire would stimulate research on tranquilizer misuse.

Research about the association of knowledge and attitudes with practices (KAP) of non-medical tranquilizer use is scarce. We compared findings from cross-sectional and longitudinal approaches in a KAP-based study on non-medical tranquilizer use in Spain using data collected from the same population. Eight-hundred forty-seven participants completed a validated KAP questionnaire at baseline and were then followed-up bimonthly for one year for episodes of non-medical tranquilizer use. Non-medical use was defined as unprescribed use, non-adherence to treatment, storage/sharing of tranquilizers, or a combination of those practices. Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using logistic regression from cross-sectional data and generalized linear mixed models for repeated measures in the longitudinal approach. Only the longitudinal approach showed that limited knowledge about the effect of tranquilizers on behaviour [OR: 3.24 (95% CI: 1.12–9.38)] and about the negative effect of their excessive consumption [OR: 4.12 (95% CI: 1.5–11.33)] is associated with storing/sharing tranquilizers. Both cross-sectional and longitudinal analyses indicated that personal attitudes towards tranquilizers and attitudes towards healthcare providers are associated with non-medical tranquilizer use, yet with different magnitude of associations. Differences between the two approaches were also observed for individual types of non-medical use. Certain discrepancies exist between findings from longitudinal and cross-sectional approaches on KAP of non-medical tranquilizer use. KAP studies are the backbone for designing and evaluating prevention programs on non-medical tranquilizer use, and hence choosing a proper study design, scrutinizing the associated biases, and carefully interpreting findings from those studies are required.

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 BT's work is funded by a Grant from the Regional Ministry of Education, Universities, and Vocational Training, Santiago de Compostela, Spain, ED431C 2018/20. SI

Purpose The aim of this study was to perform a systematic review and meta-analysis of studies performed in primary care centers and hospital facilities that evaluated the effectiveness of computerized clinical decision support systems (CDSSs) in decision making on the prescription of any given antibiotic. Methods We conducted a search of the MEDLINE and EMBASE databases. A meta-analysis was then conducted of all variables with results reported in >2 studies. Findings A total of 42 of the 46 studies included in the review identified a statistically significant advantage for CDSSs in ≥1 study variables. The effect of CDSSs on the percentage accuracy of the antibiotic spectrum prescribed empirically with respect to the microbial agent's susceptibility, which is one of the most frequently studied outcome variables, was examined in 7 studies, all undertaken in hospital settings. In all these studies but one, CDSSs resulted in a statistically significant increase in percentage accuracy. The other study variables present in >2 studies had more inconsistent results. Although the results of the meta-analysis of the variables percentage accuracy, antibiotic prescription rate in hospital, percentage adherence to antibiotic prescription guidelines in primary care or hospital, and percentage of inappropriate prescriptions for antibiotics in primary care were statistically significantly favorable to CDSSs; in the case of hospital length of stay and mortality, they were favorable although not statistically significantly. Implications CDSSs appear to be useful for variables such as the percentage of appropriate empirical treatment in the hospital setting or to induce changes in antibiotics prescription rate. Even so, more better quality studies are required to draw clearer conclusions in respect of morbidity and mortality outcome variables and other settings.

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 SI

Cross-sectional studies on the association between knowledge, attitudes, and practices of antibiotic misuse are abundant. Conversely, longitudinal studies are unavailable. The objective of this study was to compare findings from cross-sectional and longitudinal data analyses of the same study on knowledge and attitudes related to practices of antibiotic misuse in the general adult population. A validated knowledge, attitudes, and practices questionnaire was self-administered at baseline and participants were followed up bimonthly. Logistic regression was used on baseline data to compute adjusted odds ratios in the cross-sectional data analysis. In the longitudinal approach, Poisson regression and generalized linear mixed models were used to estimate adjusted incidence rate ratios and adjusted odds ratios, respectively. Seven hundred and forty-seven adults completed the baseline and the follow-up questionnaires. In the cross-sectional analysis, 78 participants misused antibiotics and strong associations were observed between agreement with various knowledge and attitudes statements and antibiotic misuse practices, with odds ratios between 1.94 and 5.66. In the longitudinal data analysis using Poisson regression, 46 events of antibiotic misuse were detected. No associations were observed between knowledge, attitudes, and misuse practices, except for two statements about the preference of storing antibiotics [adjusted incidence rate ratio: 2.33 (95% confidence interval 1.20–4.54)] and taking antibiotics when getting a cold [adjusted incidence rate ratio: 2.28 (95% confidence interval 1.24–4.21)]. The magnitude of these associations was lower than that observed in the cross-sectional analysis. Findings of the generalized linear mixed-model analysis were similar to those yielded by Poisson regression. The cross-sectional and the longitudinal approaches yield divergent results in our setting. Risk of bias in both analyses should be scrutinized.

Hematologic malignancies cause more than half a million deaths every year worldwide. Analgesics were suggested as chemopreventive agents for several cancers but so far, results from individual studies about the relationship between paracetamol (acetaminophen) use and hematologic malignancies are conflicting. Therefore, we decided to perform a systematic review and meta-analysis. We retrieved studies published in any language by systematically searching Medline, Embase, Conference Proceedings Citation Index, Open Access Theses and Dissertations, and the five regional bibliographic databases of the World Health Organization until December 2020. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated according to the inverse of their variances. We performed separate analyses by histologic type. We also evaluated publication bias and assessed quality. A total of 17 study units met our inclusion criteria. The results show an association of hematologic malignancies with any paracetamol intake (OR 1.49, 95% CI 1.23–1.80) and with high paracetamol intake (OR 1.77, 95% CI 1.45–2.16). By subtype, risk was higher for multiple myeloma (OR 2.13, 95% CI 1.54–2.94) for any use and OR 3.16, 95% CI 1.96–5.10 for high intake, while risk was lower and non-significant for non-Hodgkin lymphoma. This meta-analysis provides evidence that paracetamol intake may be associated with hematologic malignancies and suggests that a dose–response effect is plausible. These results are unlikely to be due to publication bias or low quality of studies. Future research should focus on assessing the dose–response relationship.

Background: Tranquilizer misuse is insufficiently acknowledged as a public health problem despite its alarming consequences. Instruments to measure psychosocial factors related to tranquilizer misuse are lacking. We aimed to develop and validate a Knowledge, Attitude and Practice questionnaire of tranquilizer misuse by adults in Spain. Methods: The questionnaire was designed after an extensive literature review and several meetings with experts. We assessed face and content validity, and pilot tested the questionnaire. We examined its reliability by test-retest analysis in a sample of 145 adults. We distributed the questionnaire to 879 individuals, tested the construct validity through Confirmatory Factor Analysis (CFA), measured its overall reliability and determined its acceptability. Results: The Item Content Validity Index (I-CVI from 0.78 to 1.00), the Scale Content Validity Index, using the averaging method (S-CVI/Ave = 0.95) and the fact that the modified Kappa statistic for each of the Knowledge, Attitude and Practice items was equal to I-CVI demonstrated the content validity of the questionnaire. The Intra-Class Correlation coefficients for Knowledge and Attitude items were > 0.5, establishing their reliability. The Knowledge and Attitude construct was modeled using CFA and the model showed a good fit, thus establishing its validity. The overall reliability of the construct was revealed by Cronbach՚s alpha values > 0.6. The questionnaire was highly accepted (response rate = 95 % and item non-response ≤ 4%). Conclusions: The validity of the developed questionnaire was established. Its availability will stimulate the initiation of research on tranquilizer misuse and will consequently help in designing related public health interventions.

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 This work was funded by the Regional Ministry of Education, Universities and Vocational Training (Consellería de Educación, Universidades y Formación Profesional) [Grant number ED431C 2018/20], Santiago de Compostela, Spain SI

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.

Tranquilizer misuse represents a growing international public health problem with heavy social and economic consequences. We aimed to identify the psychosocial determinants of this misuse practice, focusing on modifiable factors including knowledge and attitudes towards these medications.A prospective cohort study involving 847 adults accompanying children in primary care clinics was carried out in Spain. A validated Knowledge, Attitudes and Practices (KAP) questionnaire on tranquilizer use was self-administered at baseline, and then participants were followed-up bimonthly. A misuse event was defined as unprescribed intake of tranquilizers, storing/sharing leftovers of tranquilizers, and/or not adhering to the prescribed treatment period, timing or dosage. Poisson regression models were applied to estimate adjusted Incidence Rate Ratios (IRRs) of misuse and their 95 % Confidence Intervals (CIs).Individuals' personal attitudes towards tranquilizers and treating physicians are strongly associated with the misuse of these drugs. These attitudes include: individuals' acceptance of taking tranquilizers to improve sleeping [IRR: 5.10 (95 %CI: 2.74-9.48)], to work better [IRR: 2.04 (95 %CI: 1.05-3.99)], or for recreational purposes [IRR: 1.85 (95 %CI: 1.04-3.32)]; willingness to prolong the course of tranquilizer treatment without medical consultation [IRR: 2.45 (95 %CI: 1.46-4.13)]; agreeing on storing tranquilizers for possible future need [IRR: 5.07 (95 %CI: 2.73-9.40)]; and untrusting the physician's decision about tranquilizer prescription [IRR: 1.92 (95 %CI: 1.12-3.30)]. The level of knowledge is marginally associated with tranquilizer misuse.There is a strong association between individuals' attitudes towards tranquilizers and the misuse practices of these drugs. Educational interventional studies could help reduce the incidence of tranquilizer misuse.

BackgroundAntibiotic resistance is a major public health concern. It has been associated with factors such as uncontrolled consumption, lack of knowledge, beliefs, and sociodemographic characteristics. Lebanon is characterized by high levels of antibiotic misuse, as almost half of the population self-medicates with antibiotics and over 30% of the antibiotics are dispensed without prescription. To-date, no studies determined adequately the association between knowledge, beliefs and antibiotic misuse in Lebanon.ObjectiveTo assess the association between level of knowledge and beliefs about antibiotics, and antibiotic misuse in Lebanon.MethodsWe conducted a cross-sectional study among 1,421 parents of schoolchildren using an anonymous self-administered Knowledge, Attitude and Practices questionnaire. The participants´ level of agreement with each item of knowledge and beliefs was measured using a Likert-type (0-10) scale. Misuse practices in the last month were detected through a series of questions aimed at determining the level of compliance with physicians´ instructions in terms of dosage and duration. Data were analyzed using logistic regression.Results277 participants (16%) acknowledged using antibiotics in the previous month, 41% of whom showed at least one misuse behavior. Misconceptions and beliefs about antibiotics substantially increased the odds of their misuse. For instance, participants who believed that antibiotics were effective in treating viruses, cold, or sore throat infections were twice as likely to misuse antibiotics [Adjusted Interquartile Odds Ratio (aIqOR): 2.08 (95%CI: 1.32, 3.19), aIqOR: 1.81 (95%CI: 1.41, 2.29), aIqOR: 2.19 (95%CI: 1.61, 2.93), respectively]. Parents who usually keep antibiotics at home antibiotics for future use were more likely to misuse antibiotics [aIqOR: 2.44 (95%CI: 1.68, 3.46)].ConclusionsOur findings indicate that the low level of knowledge and the existence of erroneous beliefs about antibiotics are associated with increased odds of antibiotic misuse. Key elements including rationale prescription and control of dispensing should be addressed when designing educational campaigns against antibiotic misuse.

Background: Saliva represents a promising non-invasive source of novel biomarkers for diagnosis and prognosis cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the value of saliva as an alternative liquid biopsy. Materials and methods: We performed a systematic review and meta-analysis. PubMed, Embase, LILACS and the Cochrane Library were searched to identify articles that examined the potential of salivary biomarkers for the diagnosis of malignant non-oral tumours. To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR), area under hierarchical summary receiver operating characteristic (AUC) curve, sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) using a random- or fixed-effects model. Heterogeneity and publication bias were assessed. Statistical tests were two-sided. Results: One hundred fifty-five study units from 29 articles with 11,153 subjects were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.76 (95% confidence intervals (CI), 0.74–0.77), 0.76 (95% CI, 0.75–0.77), 3.22 (95% CI, 2.92–3.55), 0.31 (95% CI, 0.28–0.34), 13.42 (95% CI, 12.28–15.96) and 0.85 (95% CI, 0.84–0.87), respectively. Conclusion: Salivary biomarkers may be potentially used for non-invasive diagnosis of malignant non-oral tumours.Key messagesThis meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the role of saliva as an alternative liquid biopsy.Salivary biomarkers showed 85% accuracy for cancer distant to the oral cavity.Saliva represents a promising non-invasive source of novel biomarkers in cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the role of saliva as an alternative liquid biopsy. Salivary biomarkers showed 85% accuracy for cancer distant to the oral cavity. Saliva represents a promising non-invasive source of novel biomarkers in cancer.

Macrolides are widely used during pregnancy; however, their fetal safety remains uncertain. We performed a meta-analysis to assess the relation between prenatal exposure to macrolides and occurrence of congenital malformations. We searched MEDLINE, EMBASE, and other databases until June 12, 2019. We assessed the quality of the studies and checked for heterogeneity and publication bias. We performed three different analyses and compared the effect of macrolides with each of the following unexposed populations: Group 1: babies unexposed to any medicine before birth, Group 2: babies exposed to non-macrolide antibiotics/non-teratogens, and Group 3: mixed population of the first and second comparators. A weak association between macrolides and congenital malformation of any type was observed when macrolides were compared with the mixed population (ORgroup 3 1.06 [95% CI 1.01–1.10]). Subgroup analysis showed that this weak association is restricted to fetus exposure in the first trimester of pregnancy (OR 1.06 [95% CI 1.01–1.11]) and to cohort studies (OR 1.07 [95% CI 1.02–1.13]). Digestive system malformations were found to be slightly associated with prenatal exposure to macrolides (ORgroup 3 1.14 [95% CI 1.02–1.26]). The musculoskeletal system was also found to be potentially affected (ORgroup 2 1.21 [95% CI 1.08–1.35] and ORgroup 3 1.15 [95% CI 1.05–1.26]). European studies showed a slightly stronger association than American studies in these two comparisons. Our study suggests a weak association between prenatal use of macrolides and congenital malformations, limited to exposure in early pregnancy, and musculoskeletal and digestive systems. In addition to studies with a larger control of confounding, risk–benefit research is needed to determine the usefulness of macrolides during pregnancy.

Background: Only a 5% improvement in overall survival to oral cancer has been achieved in the last 20 years. Almost half of all oral carcinomas are diagnosed at advanced stages essentially due to delay in the diagnosis. Objective of the review: to examine the relative length of the patient and primary care intervals in symptomatic oral cancer. Type of review: Quantitative systematic review. Search strategy: ((oral cancer OR oral squamous cell carcinoma OR oropharyngeal cancer) AND (time interval OR diagnostic delay)). Evaluation method: we computed 5 measures (patient, primary care, diagnosis, total diagnosis, and total treatment intervals). Most studies did not provide any dispersion measure. We then used the sample size of each study to compute a weighted average of the mean intervals. When the median was provided, we assumed normality of the distribution of the means and used the median as a proxy of the mean. Results: A total of 1,089 articles were identified and 22 met the inclusion criteria, reporting on 2710 patients from Europe, USA, India, Australia, Japan, Argentina, and Iran. The weighted average of patient interval was 80.3 days. Primary care interval was five times shorter: 15.8 days. The diagnostic interval was appreciably shorter (47.9 days) when compared with the patient interval during symptomatic period. Conclusions: Patient interval represents the major component of waiting times since the detection of the first signs/symptoms to the definitive diagnosis of oral cancer. Thus, strategies focused on high-risk patients should be prioritised. Interventions aimed at optimising the health systems should be implemented by monitoring and facilitating diagnostic and treatment pathways of oral cancer patients. This article is protected by copyright. All rights reserved.

Evidence on drug safety obtained from randomised clinical trials is very limited due to, among other reasons, their relatively small sample size. Hence, combining the results of available studies can prove particularly useful. This paper reviews the different data sources for summarising drug safety outcomes, according to study design, publication of data, and origin of the information. It then discusses the various types of overviews that can be used in the study of treatment harms, focusing on meta-analyses of aggregate data and meta-analyses of individual patient data, with their advantages and drawbacks, such as publication bias and heterogeneity. Although the different approaches available for combining the results are of great utility in assessing treatment harms, none of them is free from limitations. Therefore, it might be appropriate to perform an analysis of sensitivity to assess whether the results are sensitive to the technique that has been used.

Objective : To assess whether the psychological variables perceived stress, neuroticism and coping strategies, are associated with Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Syndrome (PMDD). Design : Case-control study with incident cases using the Spanish public healthcare system. Setting 3 major public hospitals and one family counseling and planning center. Population Women consulting for troubles related to menstruation and for other motives such as screening for uterine cancer, contraception counselling or desire for pregnancy. Methods : Logistic regression. Main outcome measures : Odds of PMS and PMDD. Results : 285 PMS and 285 age-matched controls, as well as 88 PMDD cases and 176 controls participated in the study. Medium and high levels of perceived stress were associated with an increase in the odds of PMS (Odds Ratio (OR) = 2.49; 95%CI: 1.41–4.39 and OR = 4.90; 95%CI: 2.70–8.89, respectively). For PMDD the results were: OR = 2.61; 95%CI: 1.35–5.05 and OR = 5.79; 95%CI: 2.63–12.76, respectively. Subjects with medium and high levels of neuroticism were also at higher odds of suffering from PMS (OR = 2.53; 95%CI: 1.06–6.06 and OR = 8.05; 95%CI: 3.07–2.12, respectively). For PMDD, the results were OR = 3.70; 95%CI: 1.27–10.77 and 5.73: 95%CI: 1.96–16.77, respectively. High levels in the large majority of coping strategies were also associated with increased odds of PMS and PMDD. Conclusions : Psychological factors including perceived stress, neuroticism and coping strategies are strongly related to PMS/PMDD. This association is unlikely to be due to confounding or misclassification bias. A reverse causation process cannot be ruled out although its likelihood is remote. SI

Background:Allergic rhinitis has been suspected to be a risk factor for asthma in several studiesbut this association is notfirmly established. The objective of this study was to synthesize theevidence of the association between allergic rhinitis and the risk of asthma through a systematicreview and meta-analysis.Methods:We performed a search in Medline, Scopus, ISI Proceedings databases and otherdatabases from inception until February 2019, followed by manual search to identify potentiallyrelevant case-control and cohort studies that reported relative risk estimates and confidence in-tervals of the association between allergic rhinitis and asthma. Cross-sectional studies wereexcluded. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated usingfixedand random effects models and quality of studies was assessed through a modified version of theNewcastle-Ottawa scale. Results:Twenty-nine eligible studies, 22 cohort and 7 case-control studies, with a total of 274489subjects, were included in the meta-analysis. The results show that history of allergic rhinitis issignificantly associated with the occurrence of asthma (OR¼3.82; 95% CI: 2.92–4.99). Europeanstudies showed a stronger association (OR¼4.35; (95% CI: 3.12–6.06) than non-European studies(OR¼2.75; 95% CI: 2.16–3.50), and case-control studies showed a stronger association(OR¼4.71; 95% CI: 3.58–6.17) than cohort studies (OR¼3.42; 95% CI: 2.60–4.50). Conclusions:This meta-analysis shows that allergic rhinitis is strongly associated with asthma.Further prospective studies on the effect of treatment of allergic rhinitis on the development ofasthma are needed. Relief of airway allergic manifestations may need dual control of allergicrhinitis and asthma. Dr Tohidinik’s scientific stay at the University of Santiago de Compostela was funded through the Research Excellence Programme USC – IRAN. Dr Takkouche’s work is funded by Grant ED431C 2018/20 from the Regional Ministry of Education, Universities and Vocational Training (Consellería de Educación, Universidades y Formación Profesional). Santiago de Compostela, Spain SI

Several observational studies have suggested an association between periodontitis and cerebral ischemia. This meta-analysis aimed to investigate whether this link exists, and if so, the degree to which it is significant. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline for systematic review was used. The search strategy included using electronic databases and hand searching works published up to March 2015. MEDLINE via PubMed, EMBASE, Proceedings Web of Science and Current Contents Connect were searched by two independent reviewers. Case-control, cross-sectional or cohort studies including patients with measures of periodontitis and ischemic stroke were eligible to be included in the analysis. Quality assessments of selected studies were performed. From a total of 414 titles and abstracts, 57 potentially relevant full text papers were identified. After inclusion criteria were applied, 8 studies were included in the present systematic review (5 case-control and 3 cohort studies). Although it was not the intention, cross-sectional studies were excluded due to eligibility criteria were not accomplished. Therefore, meta-analyses were conducted with data retrieved from the 8 studies included. These meta-analyses showed statistically significant association between periodontitis and ischemic stroke in both cohort pooled relative risks at 2.52 (1.77-3.58), and case-control studies pooled relative risks at 3.04 (1.10-8.43). In conclusion, the present meta-analysis demonstrated an association between periodontitis and ischemic stroke. However, well-designed prospective studies should be carried out to provide robust evidence of the link between both diseases. In regards to ischemic stroke subtypes, further case-control studies should be carried out to investigate whether there is any association between the different subtypes of cerebral infarcts and periodontitis.

A systematic search of MEDLINE, Embase, and Proceedings Web of Science was undertaken to assess the prevalence of the posterior superior alveolar artery (PSAA) in the lateral sinus wall in sinus lift patients, as identified using computed tomography (CT)/cone beam computed tomography (CBCT). For inclusion, the article had to report PSAA detection in the bony wall using CT and/or CBCT in patients with subsinus edentulism. Studies on post-mortem findings, mixed samples (living and cadaveric), those presenting pooled results only, or studies performed for a sinus pathology were excluded. Heterogeneity was checked using an adapted version of the DerSimonian and Laird Q test, and quantified by calculating the proportion of the total variance due to between-study variance (Ri statistic). Eight hundred and eleven single papers were reviewed and filtered according to the inclusion/exclusion criteria. Ten studies were selected (1647 patients and 2740 maxillary sinuses (study unit)). The pooled prevalence of PSAA was 62.02 (95% confidence interval (CI) 46.33-77.71). CBCT studies detected PSAA more frequently (78.12, 95% CI 61.25-94.98) than CT studies (51.19, 95% CI 42.33-60.05). Conventional CT revealed thicker arteries than CBCT. It is concluded that PSAA detection is more frequent when CBCT explorations are used. Additional comparative studies controlling for potential confounding factors are needed to ascertain the actual diagnostic value of radiographic explorations for assessing the PSAA prior to sinus floor elevation procedures.

Dear Editor,We read with interest the comment by Lu and Wang [1] concerning the potential inclusion of duplicate articles in our meta-analysis [2]. The first article by Xie et al.[2] included 32 su...

In 2003, FDA approved Omalizumab for the treatment of severe allergic asthma. This mAb recognizes IgE and blocks its binding to basophils and mast cells, attenuating FceRI signalling. Nevertheless, its effect on T helper (Th) subsets like regulatory (Tregs) or effector (Teff) cells remains poorly described. To address this issue peripheral blood samples were drawn from three groups of adults (n= 106): Healthy controls (HC; n= 32) and clinically stable allergic asthmatics (n= 74), either on glucocorticoid (Omalizumab-; n= 50) or Omalizumab (Omalizumab+; n= 24) therapy. Due to the higher severity in the Omalizumab+ group and despite the biological, FEV1 (%) and FEV1/FVC (%) were still lower than those in Omalizumab- patients. Asthmatics showed higher eosinophil numbers and total IgE compared to HC, but Omalizumab did not cause their down-modulation. Flow cytometry evidenced a higher activated status (CD26) in Th cells from asthmatics that was not affected by Omalizumab. In contrast, the increment of “terminally differentiated” Teff percentages in Omalizumab- patients compared to HC was almost lost in the Omalizumab+ group. The biological therapy did not alter the percentage of circulating Treg cells or levels of serum TGFβ1 but led to a significant increment in the percentage of GARP+ cells within Treg and “terminally differentiated” Teff compared to HC. GARP is a receptor for latent TGFβ1 and a Treg activation marker. Therefore, apart from the actions of Omalizumab on mast cells and basophils, an additional mechanism could be the generation of lymphocytes with enhanced regulatory function or higher susceptibility to this activity.

ObjectivePremenstrual syndrome (PMS) is a very common disorder worldwide which carries an important economic burden. We conducted a systematic review and a meta-analysis to assess the role of alcohol in the occurrence of PMS.MethodsWe searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO, the Proceedings database and the Open Access Thesis and Dissertations (OATD) from inception to May 2017. We also reviewed the references of every article retrieved and established personal contact with researchers to trace further publications or reports. We did not include any language limitations. Studies were included if: (1) they presented original data from cohort, case-control or cross-sectional studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the exposure factors was alcohol consumption, (4) they provided estimates of odds ratios, relative risks, or any other effect measure and their confidence intervals, or enough data to calculate them.ResultsWe identified 39 studies of which 19 were eligible. Intake of alcohol was associated with a moderate increase in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32).DiscussionOur results suggest that alcohol intake presents a moderate association with PMS risk. Future studies should avoid cross-sectional designs and focus on determining whether there is a threshold of alcohol intake under which the harmful effect on PMS is non-existent.