Sleep quality as a mediator of the relation between depression and chronic pain: a systematic review and meta-analysis.

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.

Social factors and chronic pain: the modifying effect of sex in the Stockholm Public Health Cohort Study.

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.

Gastroesophageal reflux disease and asthma exacerbation: A systematic review and meta-analysis.

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.

Association between alcohol consumption and chronic pain: a systematic review and meta-analysis.

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: OR2nd quartile=0.74; 95% CI, 0.64-0.87; OR3rd quartile=0.67; 95% CI, 0.53-0.86; and OR4th 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.

Diabetes mellitus and oral lichen planus: A systematic review and meta-analysis.

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.

Sleep quality and risk of recurrent aphthous ulcers: A Spanish cohort study.

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.

Immunohistochemical analysis of epithelium adjacent to lip cancer: A meta-analysis.

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.

Socioeconomic status and occurrence of chronic pain: a meta-analysis.

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.

Blood eosinophil count as predictor of asthma exacerbation. A meta-analysis.

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.

Social factors and pain worsening: a retrospective cohort study.

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.

Prognostic value of CAIX expression in oral squamous cell carcinoma: a systematic review and meta-analysis.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein considered as a predictor for oral squamous cell carcinoma (OSCC) biological behaviour. Nevertheless, this prognostic value is still yet to be validated. We aim to quantify prognostic significance of CAIX overexpression in OSCC by meta-analysis. We performed searches in MEDLINE, EMBASE, SCOPUS, WOS, WHO'S databases, CPCI, and OATD from inception to August 2019. Overall survival (OS), disease-free survival (DFS), locoregional control (LC), and disease-specific survival (DSS) were considered as outcomes of interest. Overall 18 studies were included. CAIX overexpression was associated with worse OS (hazard ratio [HR] = 1.45 95% confidence interval [CI] 1.17-1.80) and DFS (HR = 1.98 95% CI 1.18-3.32). To the contrary, it was neither associated with LC (HR = 1.01 95% CI 0.50-2.02) nor with DSS (HR = 1.35 95% CI 0.78-2.33). Heterogeneity was negligible in all analyses except for DSS. Small studies effect was not significant for OS and DFS. This study shows that immunohistochemical CAIX assessment is a useful OSCC prognostic biomarker.

Bias in pharmacoepidemiologic studies using secondary health care databases: a scoping review.

BACKGROUND: The availability of clinical and therapeutic data drawn from medical records and administrative databases has entailed new opportunities for clinical and epidemiologic research. However, these databases present inherent limitations which may render them prone to new biases. We aimed to conduct a structured review of biases specific to observational clinical studies based on secondary databases, and to propose strategies for the mitigation of those biases. METHODS: Scoping review of the scientific literature published during the period 2000-2018 through an automated search of MEDLINE, EMBASE and Web of Science, supplemented with manually cross-checking of reference lists. We included opinion essays, methodological reviews, analyses or simulation studies, as well as letters to the editor or retractions, the principal objective of which was to highlight the existence of some type of bias in pharmacoepidemiologic studies using secondary databases. RESULTS: A total of 117 articles were included. An increasing trend in the number of publications concerning the potential limitations of secondary databases was observed over time and across medical research disciplines. Confounding was the most reported category of bias (63.2% of articles), followed by selection and measurement biases (47.0% and 46.2% respectively). Confounding by indication (32.5%), unmeasured/residual confounding (28.2%), outcome misclassification (28.2%) and "immortal time" bias (25.6%) were the subcategories most frequently mentioned. CONCLUSIONS: Suboptimal use of secondary databases in pharmacoepidemiologic studies has introduced biases in the studies, which may have led to erroneous conclusions. Methods to mitigate biases are available and must be considered in the design, analysis and interpretation phases of studies using these data sources.

Primary versus secondary source of data in observational studies and heterogeneity in meta-analyses of drug effects: a survey of major medical journals.

BACKGROUND: The data from individual observational studies included in meta-analyses of drug effects are collected either from ad hoc methods (i.e. "primary data") or databases that were established for non-research purposes (i.e. "secondary data"). The use of secondary sources may be prone to measurement bias and confounding due to over-the-counter and out-of-pocket drug consumption, or non-adherence to treatment. In fact, it has been noted that failing to consider the origin of the data as a potential cause of heterogeneity may change the conclusions of a meta-analysis. We aimed to assess to what extent the origin of data is explored as a source of heterogeneity in meta-analyses of observational studies. METHODS: We searched for meta-analyses of drugs effects published between 2012 and 2018 in general and internal medicine journals with an impact factor > 15. We evaluated, when reported, the type of data source (primary vs secondary) used in the individual observational studies included in each meta-analysis, and the exposure- and outcome-related variables included in sensitivity, subgroup or meta-regression analyses. RESULTS: We found 217 articles, 23 of which fulfilled our eligibility criteria. Eight meta-analyses (8/23, 34.8%) reported the source of data. Three meta-analyses (3/23, 13.0%) included the method of outcome assessment as a variable in the analysis of heterogeneity, and only one compared and discussed the results considering the different sources of data (primary vs secondary). CONCLUSIONS: In meta-analyses of drug effects published in seven high impact general medicine journals, the origin of the data, either primary or secondary, is underexplored as a source of heterogeneity.

Is Periodontal Disease Associated with Alzheimer's Disease? A Systematic Review with Meta-Analysis.

BACKGROUND: In the last decade, several observational studies have suggested that there exists an association between periodontal disease (PD) and Alzheimer's disease (AD). The aim of this systematic review was to investigate whether or not this link exists. SUMMARY: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for systematic review was used and registered at PROSPERO (CRD42016035377). The search strategy included using electronic databases and by hand searching articles published up to January 2016. MEDLINE via PubMed, EMBASE and Web of Science were searched by 2 independent reviewers. Observational studies including patients meeting criteria for both AD and PD were eligible to be included in the analysis. Quality assessment of selected studies was performed by the Newcastle-Ottawa Scale. From a total of 550 titles and abstracts, 5 studies were included (2 cross-sectional, 2 case-control and one cohort study) in the review. A fixed effects meta-analysis showed that the presence of PD is associated with the presence of AD (OR 1.69, 95% CI 1.21-2.35). When only severe forms of PD were evaluated, a significant association was also observed (OR 2.98, 95% CI 1.58-5.62). Key Messages: In the present review, a significant association was observed between PD and AD. Further studies should be carried out in order to investigate the direction of the association and factors that may confound it.

Association between periodontitis and ischemic stroke: a systematic review and meta-analysis.

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.

Active or passive exposure to tobacco smoking and allergic rhinitis, allergic dermatitis, and food allergy in adults and children: a systematic review and meta-analysis.

BACKGROUND: Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions. METHODS AND FINDINGS: We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children. We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92-1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06-1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14-1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03-1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24-1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04-1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17-1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01-1.11]). Food allergy was associated with SHS (1.43 [1.12-1.83]) when cohort studies only were examined, but not when all studies were combined. The findings are limited by the potential for confounding and bias given that most of the individual studies used a cross-sectional design. Furthermore, the studies showed a high degree of heterogeneity and the exposure and outcome measures were assessed by self-report, which may increase the potential for misclassification. CONCLUSIONS: We observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.

Neurological adverse events related to lip biopsy in patients suspicious for Sjögren's syndrome: a systematic review and prevalence meta-analysis.

OBJECTIVE: The aim of this study was to compare the prevalence of neurological complications related to lip biopsy for SS diagnosis using conventional vs minimally invasive techniques. METHODS: We performed a systematic review and prevalence meta-analysis using the search strategy [(salivary gland biopsy OR labial biopsy OR lip biopsy) AND (Sjögren)] in the MEDLINE, EMBASE and Web of Science Conference Proceedings Citation Index databases. Studies were selected if they included original data for minor salivary gland biopsy, sample size, exposure of interest (technique description), number of complications and number of affected patients. The prevalence of total and permanent neurological adverse effects was calculated. Both fixed-effects and random-effects pooled estimates were assessed. Heterogeneity was calculated using an adaptation of the DerSimonian and Laird Q test. RESULTS: Sixteen articles were selected for the study. In the minimally invasive group (n = 3), the pooled prevalence of total adverse events is almost four times higher than that in the linear incision group (n = 12) (4.73% vs. 1.20%). In contrast, the pooled prevalence of the permanent or potentially permanent neurological adverse events is 8.5 times lower in the minimally invasive technique group than in the studies using linear incisions (0.17% vs. 1.45%). CONCLUSION: With the limitations intrinsic to the potential biases in the studies included in this meta-analysis, we conclude that the minimally invasive lip biopsy technique for SS diagnosis induces fewer permanent neurological complications than conventional approaches with large linear incisions in the lower lip.

Confidence intervals for heterogeneity measures in meta-analysis.

Two methods of quantifying heterogeneity between studies in meta-analysis were studied. One method quantified the proportion of the total variance of the effect estimate due to variation between studies (RI), and the other calibrated the variance between studies to the size of the effect itself through a between-study coefficient of variation (CVB). Bootstrap and asymptotic confidence intervals for RI and CVB were derived and evaluated in an extensive simulation study that covered a wide range of scenarios likely to be encountered in practice. The best performance was given by asymptotic Wald confidence intervals developed for RI and CVB. The use of these heterogeneity measures together with their confidence intervals was illustrated in 5 typical meta-analyses. A new user-friendly SAS macro (SAS Institute, Inc., Cary, North Carolina) is provided to implement these methods for routine use and can be downloaded at the last author's website.

Factors Contributing to the Link between Physical Well-Being and Chronic Pain in Young People from Galicia, Northwest Spain.

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 (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). 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.

Education level and misuse of antibiotics in the general population: a systematic review and dose-response meta-analysis.

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.