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.
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.
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.
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.
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.
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.
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.
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.
Allergic rhinitis has been suspected to be a risk factor for asthma in several studies but this association is not firmly established. The objective of this study was to synthesize the evidence of ...the association between allergic rhinitis and the risk of asthma through a systematic review and meta-analysis.
We performed a search in Medline, Scopus, ISI Proceedings databases and other databases from inception until February 2019, followed by manual search to identify potentially relevant case-control and cohort studies that reported relative risk estimates and confidence intervals of the association between allergic rhinitis and asthma. Cross-sectional studies were excluded. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed and random effects models and quality of studies was assessed through a modified version of the Newcastle-Ottawa scale.
Twenty-nine eligible studies, 22 cohort and 7 case-control studies, with a total of 274489 subjects, were included in the meta-analysis. The results show that history of allergic rhinitis is significantly associated with the occurrence of asthma (OR = 3.82; 95% CI: 2.92–4.99). European studies showed a stronger association (OR = 4.35; (95% CI: 3.12–6.06) than non-European studies (OR = 2.75; 95% CI: 2.16–3.50), and case-control studies showed a stronger association (OR = 4.71; 95% CI: 3.58–6.17) than cohort studies (OR = 3.42; 95% CI: 2.60–4.50).
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 of asthma are needed. Relief of airway allergic manifestations may need dual control of allergic rhinitis and asthma.
PROSPERO database with registration number CRD42017055156.
In the last two decades, the number of studies focused on the mediators connecting insecure attachment with Eating Disorders (EDs), at both clinical and sub-clinical level, has considerably ...increased. However, there has not been a systematic synthesis of this literature to date. To fill this gap, the current meta-analytic review aimed at identifying and quantifying the extent to which mediators contribute to the explanation of this relationship. The present study was registered with PROSPERO (CRD42017076807). A comprehensive search process in seven different electronic databases retrieved 24 studies that examined how insecure attachment leads to ED symptoms through mediation analysis. Standardized regression coefficients of the indirect and total paths of 21 mediation models were pooled. Studies were coded and ranked for quality. We found evidence to show that maladaptive emotion regulation and depressive symptoms had the highest effect size for mediation (mediation ratio PM = 0.71). Further, body dissatisfaction, neuroticism, perfectionism, mindfulness and social comparison had significant, but moderate to low mediating effects (PM = 0.21-0.58). The methodological quality of these studies was mostly low to moderate and potential areas for development were highlighted. Our findings support the direct targeting of these psychological constructs in prevention programs and treatment of EDs. Future investigations addressing the time sequence between the variables will provide valuable clues to untangle the prospective contribution of each variable on the development and maintenance of eating pathology.
Background Breast cancer is one of the leading causes of mortality among women. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk for breast cancer, but ...results from these studies of the association have been inconsistent. Methods Studies that examined the association between risk of breast cancer and use of NSAIDs, including aspirin and ibuprofen, that were published between January 1, 1966, and July 1, 2008, were identified using Medline, EMBASE, and other databases. We performed meta-analysis by pooling studies according to the inverse of their variances and performed separate analyses of studies pooled according to aspirin use and ibuprofen use. We evaluated publication bias and study quality. Results A total of 38 studies (16 case–control studies, 18 cohort studies, 3 case–control studies nested in well-defined cohorts, and 1 clinical trial) that included 2 788 715 subjects were identified. The results of these studies suggest that overall, NSAID use was associated with reduced risk for breast cancer (relative risk RR = 0.88, 95% confidence interval CI = 0.84 to 0.93). Specific analyses for aspirin (RR = 0.87, 95% CI = 0.82 to 0.92) and ibuprofen (RR = 0.79, 95% CI = 0.64 to 0.97) yielded similar results. Conclusions This meta-analysis provides evidence that NSAID use is associated with reduced risk for breast cancer. Future research should include careful evaluation of the biologic mechanisms involved in the relationship between NSAIDs and breast cancer.
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, crosssectional or cohort studies including patients with measures of periodontitis and ischémie 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 ischémie 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.
To assess whether the psychological variables perceived stress, neuroticism and coping strategies, are associated with Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Syndrome (PMDD).
...Case-control study with incident cases using the Spanish public healthcare system.
3 major public hospitals and one family counseling and planning center.
Women consulting for troubles related to menstruation and for other motives such as screening for uterine cancer, contraception counselling or desire for pregnancy.
Logistic regression.
Odds of PMS and PMDD.
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.
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.
Background Antibiotic 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. Objective To assess the association between level of knowledge and beliefs about antibiotics, and antibiotic misuse in Lebanon. Methods We 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. Results 277 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). Conclusions Our 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.
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.