A meta-analysis of observational studies on anticholinergic burden and fracture risk: evaluation of conventional burden scales

Abstract Background Anticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales. Methods Primary literature was retrieved from PubMed (1966 to March, 2021), the Cochrane Library (1974 to March, 2021), Scopus (1970 to March, 2021), and Ichushi-web (1983 to March, 2021). Cohort and case-control studies that evaluated the association between any fracture and anticholinergic drugs were included. Additionally, we included studies in which patients were administered anticholinergic drugs included on the anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale, or drug burden index-anticholinergic component. Random effects models were used to calculate pooled relative risk (RR) and 95% confidence interval (CI) due to heterogeneity among the studies. Publication bias was examined by funnel plots and the Begg’s test. Results A total of 49 datasets from 10 studies were included in the meta-analysis. Six of the 10 studies included only patients aged over 65 years, who accounted for 93% of the total study population (453,186/487,247). Meta-analysis indicated a positive relationship between use of anticholinergic drugs and fracture risk, regardless of the anticholinergic burden scale used. However, the relationship between anticholinergic burden and fracture risk varied depending on the scale used. Fracture risk increased linearly with increasing anticholinergic burden measured using ARS. ARS 1 point was associated with 28% increase in fracture risk, ARS 1–2 point(s) with 39%, ARS 2 points with 54%, ARS 3 points with 66%, and ARS ≥ 4 points with 77%. On the other hand, ACB 1 point and ACB 2 points were associated with similar fracture risk (pooled RR [95% CI]: overall; 1.28 [1.18–1.39], 1 point; 1.12 [1.06–1.18], 2 points; 1.15 [1.08–1.23]). Conclusions This result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.

Download Full-text

Quality of anticholinergic burden scales and their impact on clinical outcomes: a systematic review

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-02994-x ◽

2020 ◽

Author(s):

Angela Lisibach ◽

Valérie Benelli ◽

Marco Giacomo Ceppi ◽

Karin Waldner-Knogler ◽

Chantal Csajka ◽

...

Keyword(s):

Side Effects ◽

Clinical Outcomes ◽

Validation Studies ◽

Multiple Scales ◽

Meta Analysis ◽

Anticholinergic Drug ◽

Burden Scale ◽

Newcastle Ottawa Scale ◽

Anticholinergic Burden

Abstract Purpose Older people are at risk of anticholinergic side effects due to changes affecting drug elimination and higher sensitivity to drug’s side effects. Anticholinergic burden scales (ABS) were developed to quantify the anticholinergic drug burden (ADB). We aim to identify all published ABS, to compare them systematically and to evaluate their associations with clinical outcomes. Methods We conducted a literature search in MEDLINE and EMBASE to identify all published ABS and a Web of Science citation (WoS) analysis to track validation studies implying clinical outcomes. Quality of the ABS was assessed using an adapted AGREE II tool. For the validation studies, we used the Newcastle-Ottawa Scale and the Cochrane tool Rob2.0. The validation studies were categorized into six evidence levels based on the propositions of the Oxford Center for Evidence-Based Medicine with respect to their quality. At least two researchers independently performed screening and quality assessments. Results Out of 1297 records, we identified 19 ABS and 104 validations studies. Despite differences in quality, all ABS were recommended for use. The anticholinergic cognitive burden (ACB) scale and the German anticholinergic burden scale (GABS) achieved the highest percentage in quality. Most ABS are validated, yet validation studies for newer scales are lacking. Only two studies compared eight ABS simultaneously. The four most investigated clinical outcomes delirium, cognition, mortality and falls showed contradicting results. Conclusion There is need for good quality validation studies comparing multiple scales to define the best scale and to conduct a meta-analysis for the assessment of their clinical impact.

Download Full-text

Metabolic syndrome and esophageal cancer risk: a systematic review and meta‑analysis

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00627-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jinjia Zhang ◽

Huadong Wu ◽

Rongying Wang

Keyword(s):

Metabolic Syndrome ◽

Esophageal Cancer ◽

Cancer Risk ◽

Clinical Studies ◽

Meta Analysis ◽

Cochrane Library ◽

Case Control Studies ◽

The Metabolic Syndrome ◽

Subgroup Analyses ◽

The Relationship

Abstract Objective Many clinical studies evaluating the relationship between metabolic syndrome and esophageal cancer yielded uncertain results. The purpose of this study is to systematically assess the relationship between metabolic syndrome and esophageal cancer. Methods We searched clinical studies on metabolic syndrome and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. Meta-analysis was conducted by RevMan 5.3 softwares. Results A total of four cohort studies and two case–control studies met eligibility criteria and were included in the meta-analysis. Meta-analysis using a fixed-effect model indicated that MetS was related with a higher risk of EC (OR: 1.16, 95% CI 1.08–1.25). Subgroup analyses grouped by pathological types showed that MetS was related with a higher risk of EAC (OR: 1.19, 95% CI 1.10–1.28). Subgroup analyses grouped by metabolic conditions showed hyperglycemia (OR: 1.12, 95% CI 1.03–1.21),hypertension (OR: 1.23, 95% CI 1.04–1.46), obesity (OR: 1.40, 95% CI 1.22–1.60, P < 0.05) were related with a higher risk of EAC. Conclusions Overall, our meta-analysis provides high quality evidence that metabolic syndrome was related with a higher risk of EAC. Among the individual components of the metabolic syndrome, hyperglycemia, hypertension and obesity may be the key factors.

Download Full-text

The CEBPE rs2239633 genetic polymorphism on susceptibility to childhood acute lymphoblastic leukemia: An updated meta-analysis

10.21203/rs.3.rs-39812/v1 ◽

2020 ◽

Author(s):

Jin Liu ◽

Gu Weiling ◽

Li Xueqin ◽

Xie Liang ◽

Wang Linhong ◽

...

Keyword(s):

Lymphoblastic Leukemia ◽

Meta Analysis ◽

Case Control ◽

Cochrane Library ◽

Case Control Studies ◽

Knowledge Infrastructure ◽

Random Ratio ◽

Regression Test ◽

The Impact ◽

The Relationship

Abstract Background: We performed an updated meta-analysis to clarify the relationship between the CEBPE rs2239633 polymorphism and the CALL susceptibility.Methods: All the case-control studies updated on July 31, 2019 through Web of Science, Pubmed, Cochrane Library, Embase, China Nationa Knowledge Infrastructure (CNKI) electronic database. The heterogeneity in the study was tested by the Q-test and I2, and then the random ratio or fixed effect was utilized to merge the odds ratios (OR) and 95% confidence interval (CI). To estimate the impact of individual studies on aggregate estimates, we performed sensitivity analysis. Using funnel plot and Begger’s regression test investigated the publication bias. All data Statistical analyses were performed using Stata 12.0.Results: A total of 23442 participants (7014 patients; 16428 controls) were included in twenty case-control studies selected. There was no association of CEBPE rs2239633 polymorphism with CALL (CC vs CT + TT: OR = 1.08, 95% CI = 0.94 –1.26; CC + CT vs TT: OR = 1.10, 95% CI = 0.94–1.30; C vs T: OR =1.02, 95% CI = 0.92–1.13). In the subgroup analysis by ethnicity, no significant association of this polymorphism and CALL risks among Asia and Caucasian populations for the comparison of CC vs CT + TT, CC + CT vs TT and C vs T genetic models .Conclusion: This meta-analysis did not find the CEBPE rs2239633 polymorphism can increase and decrease the risk of susceptibility to CALL.

Download Full-text

Birth Weight and Subsequent Risk of Total Leukemia and Acute Leukemia: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2021.722471 ◽

2021 ◽

Vol 9 ◽

Author(s):

Hailuo Che ◽

Dunmei Long ◽

Qian Sun ◽

Lina Wang ◽

Yunbin Li

Keyword(s):

Birth Weight ◽

Cohort Studies ◽

Meta Analysis ◽

Pooled Analysis ◽

Case Control ◽

Cochrane Library ◽

Case Control Studies ◽

Increased Risk ◽

The Relationship ◽

Dose Dependent

Objective: Birth weight, an important indicator of fetal nutrition and degree of development, may affect the risk of subsequent leukemia. At present, little is known about the effect of birth weight on acute myeloid leukemia (AML) and whether there is a dose-dependent relationship of birth weight with acute lymphoid leukemia (ALL) and AML. To address these questions, the present work aimed to systematically investigate the relationship between birth weight and the risk of subsequent leukemia based on the current epidemiological studiesMethods: Relevant studies were systematically retrieved from electronic databases PubMed, Embase, and Cochrane Library, from inception to May 15th, 2021. Finally, 28 studies (including 21 case-control studies and 7 cohort studies) were included for the final meta-analysis. Results in cohort studies were performed by risk ratios (RRs), while those in case-control studies by odds ratios (ORs), and all results were assessed by adopting the random-effect model. Besides, a dose-dependent analysis was conducted based on the cohort studies.Results: Compared with the population with normal birth weight (NBW), the population with high birth weight (HBW) might have an increased risk of leukemia (OR 1.33, 95%CI 1.20–1.49; I2 0%). Meanwhile, low birth weight (LBW) was associated with a decreased risk of ALL, as evidenced from the pooled analysis of case-control studies (OR 0.83, 95% CI 0.75–0.92; I2 23.3%). However, relative to NBW population, the HBW population might have an increased risk of ALL (OR 1.28, 95% CI 1.20–1.35; I2 7%). There was no obvious evidence supporting the relationship between LBW and the risk of AML from the pooled analysis of case-control studies (OR, 1.11 95% CI 0.87–1.42; I2 31.7%).Conclusions: Overall, in children and young adults, HBW population may be associated with the risks of subsequent leukemia and AML relative to NBW population, but the supporting dose-dependent evidence is lacking. In addition, compared with NBW population, there is stronger evidence supporting a significantly increased risk of subsequent ALL in HBW population, and a decreased risk in LBW population in a dose-dependent manner. More prospective studies with large samples are warranted in the future to validate and complement these findings.

Download Full-text

Thiazide Use and Fracture Risk: An updated Bayesian Meta-Analysis

Scientific Reports ◽

10.1038/s41598-019-56108-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Tesfaye Getachew Charkos ◽

Yawen Liu ◽

Lina Jin ◽

Shuman Yang

Keyword(s):

Cohort Studies ◽

Fracture Risk ◽

Protective Factor ◽

Meta Analysis ◽

Random Effect Model ◽

Experimental Studies ◽

Case Control ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Case Control Studies

AbstractThe association between thiazide use and fracture risk is still controversial. We conducted an updated meta-analysis on the association between thiazide use and fracture risk. We systematically searched PubMed, Embase, and Cochrane library databases for all types of human studies, including observational and experimental studies that were published up until July 2019. We also manually searched the reference lists of relevant studies. The pooled relative risks (RRs) with 95% credible interval (CrI) were calculated using a Bayesian hierarchical random effect model. A total of 19 case-control (N = 496,568 subjects) and 21 cohort studies (N = 4,418,602 subjects) were included in this meta-analysis. The pooled RR for fractures associated with thiazide use was 0.87 (95% CrI: 0.70–0.99) in case-control and 0.95 (95% CrI: 0.85–1.08) in cohort studies. The probabilities that thiazide use reduces any fracture risk by more than 0% were 93% in case-control studies and 72% in cohort studies. Significant heterogeneity was found for both case-control (p < 0.001, I2 = 75%) and cohort studies (p < 0.001, I2 = 97.2%). Thiazide use was associated with reduced fracture risk in case-control studies, but not in cohort studies. The associations demonstrated in case-control studies might be driven by inherent biases, such as selection bias and recall bias. Thus, thiazide use may not be a protective factor for fractures.

Download Full-text

The association of GATM polymorphism with statin-induced myopathy: a systematic review and meta-analysis

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-03019-3 ◽

2020 ◽

Author(s):

Mengyuan Liu ◽

Fangfang Fan ◽

Yan Zhang ◽

Jianping Li

Keyword(s):

Web Of Science ◽

Meta Analysis ◽

Case Control ◽

Cochrane Library ◽

Inclusion Criteria ◽

Case Control Studies ◽

Pooled Data ◽

Statin Adherence ◽

The Relationship ◽

Pharmacogenomics Biomarker

Abstract Purpose Statin-induced myopathy (SIM) is the commonest reason for discontinuation of statin therapy. The aim of this present meta-analysis is to assess the relationship between glycine amidinotransferase gene (GATM) polymorphism and risk of SIM. Methods MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched systematically for case-control studies investigating the relationship between GATM polymorphism and SIM. Retrieved articles were carefully reviewed and assessed according to the inclusion criteria. Associations were assessed in pooled data by calculating odds ratio with 95% confidence intervals. Subgroup analysis was performed according to comedications and severity of SIM. Results Six studies with 707 cases and 2321 controls were included in this meta-analysis. GATM rs9806699 G>A was associated with decreased risk of SIM (OR = 0.80, 95% CI 0.68–0.94, P = 0.006). This association remained significant in the subgroup with fibrates or niacin excluded. However, the association of rs9806699 G>A with severe SIM was not significant. In addition, another two variations at GATM, rs1719247 C>T, and rs1346268 T>C were also associated with declined risk of SIM. Conclusions GATM polymorphism including rs9806699 G>A, rs1719247 C>T, and rs1346268 T>C may be protective factors of SIM. GATM rs9806699 G>A may only exert protective effect on mild SIM cases. Our meta-analysis indicates that GATM polymorphism may represent a pharmacogenomics biomarker for predicting incidence of SIM, which contributes to risk stratification and optimizing statin adherence.

Download Full-text

Dietary patterns and risk of bladder cancer: a systematic review and meta-analysis

BMC Public Health ◽

10.1186/s12889-022-12516-2 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Mostafa Dianatinasab ◽

Elaheh Forozani ◽

Ali Akbari ◽

Nazanin Azmi ◽

Dariush Bastam ◽

...

Keyword(s):

Bladder Cancer ◽

Cohort Studies ◽

Dietary Patterns ◽

Meta Analysis ◽

Case Control ◽

Cochrane Library ◽

Case Control Studies ◽

Direct Association ◽

Protocol Registration ◽

The Relationship

Abstract Background Several studies have investigated the relationship between dietary patterns and the risk of bladder cancer (BC) in different regions including Europe, the United States, and Asia, with no conclusive evidence. A meta-analysis was undertaken to integrate the most recent information on the relationship between a data-driven Western diet (WD), the Mediterranean diet (MD), and dietary-inflammatory-index (DII) and the risk of BC. Method We looked for published research into the relationship between dietary patterns and the incidence of BC in the PubMed/Medline, Cochrane Library, Web of Science, and Scopus databases up until February 2021. Using a multivariate random-effects model, we compared the highest and lowest categories of WD, MD and DII patterns and provided the relative risk (RR) or odds ratios (OR) and 95 percent confidence intervals (CIs) for the relevant relationships. Results The analysis comprised 12 papers that were found to be suitable after scanning the databases. Both case–control (OR 0.73, 95% CI: 0.52, 0.94; I2 = 49.9%, n = 2) and cohort studies (RR 0.93, 95% CI: 0.88, 0.97; I2 = 63%, n = 4) found a substantial inverse association between MD and BC. In addition, although cohort studies (RR 1.53, 95% CI 1.37, 1.70; I2 = 0%, n = 2) showed a direct association between WD and BC, case–control studies (OR 1.33, 95% CI 0.81, 1.88; I2 = 68.5%, n = 2) did not. In cohort studies, we found no significant association between DII and BC (RR 1.02, 95% CI 0.93, 1.12; I2 = 38.5%, n = 2). In case–control studies, however, a strong direct association between DII and BC was discovered (RR 2.04, 95% CI 1.23, 2.85; I2 = 0%, n = 2). Conclusion The current meta-analysis showed that MD and WD have protective and detrimental effects on BC risk, respectively. No significant association between DII and the risk of BC was observed. More research is still needed to confirm the findings. Additional study is warranted to better understand the etiological mechanisms underlying how different dietary patterns affect BC. Trial registration Protocol registration number:CRD42020155353. Database for protocol registration: The international prospective register of systematic reviews database (PROSPERO). Data of registration: August 2020.

Download Full-text

Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis

Current Alzheimer Research ◽

10.2174/1567205017666200317102337 ◽

2020 ◽

Vol 17 (2) ◽

pp. 105-111

Author(s):

Haitao Liu ◽

Wei Ge ◽

Wei Chen ◽

Xue Kong ◽

Weiming Jian ◽

...

Keyword(s):

Gene Polymorphism ◽

Large Scale ◽

Late Onset ◽

Meta Analysis ◽

Case Control ◽

Cochrane Library ◽

Positive Trend ◽

Case Control Studies ◽

China National Knowledge Infrastructure ◽

Aldh2 Gene

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association. Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity. Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed. Conclusions: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.

Download Full-text

Accuracy of angiopoietin-2 for predicting organ failure in patients with acute pancreatitis: a systematic review and meta-analysis

Journal of International Medical Research ◽

10.1177/0300060520986708 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052098670

Author(s):

Yongcai Lv ◽

Yanhua Yao ◽

Qi Liu ◽

Jingjing Lei

Keyword(s):

Acute Pancreatitis ◽

Organ Failure ◽

Meta Analysis ◽

Characteristic Curve ◽

Diagnostic Odds Ratio ◽

Cochrane Library ◽

Case Control Studies ◽

Likelihood Ratios ◽

Summary Receiver Operating Characteristic ◽

Angiopoietin 2

Objective Our aim was to assess the accuracy of angiopoietin-2 (Ang-2) as a prognostic marker for acute pancreatitis (AP) with organ failure (OF). Methods We undertook a systematic search of the PubMed, Cochrane Library, Embase, Chinese Journals Full-text, Wanfang, China Biology Medicine disc, and Weipu databases to identify eligible cohort studies on the predictive value of Ang-2 for AP with OF. The main outcome measures were sensitivity and specificity. The effects were pooled using a bivariate mixed-effects model. Results Six articles with seven case-control studies (n = 650) were included. Pooled sensitivity, specificity, and positive and negative likelihood ratios with 95% confidence intervals (CI) for AP with OF were 0.93 (95%CI: 0.75–0.99), 0.85 (95%CI: 0.75–0.92), 6.40 (95%CI: 3.36–12.19), and 0.08 (95%CI: 0.02–0.36), respectively. The area under the summary receiver operating characteristic curve was 0.95 (95%CI: 0.92–0.96), and the diagnostic odds ratio was 83.18 (95%CI: 11.50–623.17). Subgroup analysis showed that admission time of AP onset (< or ≥24 hours) was a source of overall heterogeneity. Sensitivity analysis supported this finding. Conclusion Ang-2 had high diagnostic accuracy for AP with OF; the best prediction of Ang-2 may be 24 to 72 hours after onset of AP.

Download Full-text

Appendectomy Does Not Increase the Risk of Future Emergence of Parkinson’s Disease: A Meta-analysis

The American Surgeon ◽

10.1177/0003134821989034 ◽

2021 ◽

pp. 000313482198903

Author(s):

Mitsuru Ishizuka ◽

Norisuke Shibuya ◽

Kazutoshi Takagi ◽

Hiroyuki Hachiya ◽

Kazuma Tago ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Meta Analysis ◽

Cochrane Library ◽

Random Effects Models ◽

Significant Difference ◽

The Cochrane Library ◽

The Impact ◽

The Relationship ◽

Observation Period

Objective To explore the impact of appendectomy history on emergence of Parkinson’s disease (PD). Background Although there are several studies to investigate the relationship between appendectomy history and emergence of PD, the results are still controversial. Methods We performed a comprehensive electronic search of the literature (the Cochrane Library, PubMed, and the Web of Science) up to April 2020 to identify studies that had employed databases allowing comparison of emergence of PD between patients with and those without appendectomy history. To integrate the impact of appendectomy history on emergence of PD, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected studies, and heterogeneity was analyzed using I2 statistics. Results Four studies involving a total of 6 080 710 patients were included in this meta-analysis. Among 1 470 613 patients with appendectomy history, 1845 (.13%) had emergences of PD during the observation period, whereas among 4 610 097 patients without appendectomy history, 6743 (.15%) had emergences of PD during the observation period. These results revealed that patients with appendectomy history and without appendectomy had almost the same emergence of PD (RR, 1.02; 95% CI, .87-1.20; P = .83; I2 = 87%). Conclusion This meta-analysis has demonstrated that there was no significant difference in emergence of PD between patients with and those without appendectomy history.

Download Full-text